Physiology最新文献

{"title":"Alterations of Mitochondrial Respiratory Function in Isolated Nephron Segments of Dahl Salt-Sensitive Rats in Salt-Induced Hypertension","authors":"R. Dash, Chun Yang, S. Shimada, N. Zheleznova, A. Cowley","doi":"10.1152/physiol.2023.38.s1.5732709","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732709","url":null,"abstract":"Rationale: Mammalian kidneys actively reabsorb nearly 99% of the glomerular filtrate to maintain body fluid and solute homeostasis which requires a great amount of ATP generation and O2 consumption to meet these demands. A high salt diet increases glomerular filtration of Na+ and places a high metabolic demand on the renal tubules to reabsorb more Na+in order for the organism to maintain Na+ balance. Dahl salt-sensitive (SS) rats which mimic the human condition become hypertensive when fed a high salt diet. They are also known to reabsorb greater amounts of Na+ in the proximal tubules (PT) and medullary thick ascending limbs (mTAL) thereby requiring greater ATP production and O2consumption. We hypothesized that the mitochondrial respiratory function of the PT and mTAL would be altered when SS rats are fed a high salt diet in ways that reduce the ability of the kidney to function efficiency thereby leading to salt-induced hypertension. Method: Agilent Seahorse XF96 Extracellular Flux Analyzer was used to assess mitochondrial respiratory function in freshly bulk isolated PT and mTAL from age-matched SS rats during the development of salt-induced hypertension fed with 0.4% NaCl diet (low salt; LS) or 4.0% NaCl diet (high salt; HS) for 7, 14, and 21 days. The Seahorse “Cell Mito Stress Test Protocol” was slightly modified with a substrate addition step to assess the segment-specific and substrate-dependent tubular O2 consumption rate (OCR) under different perturbations, which was used to determine alterations in different mitochondrial respiratory parameters, including H+ leak and ATP production dependent OCR, in the PT and mTAL during the development of salt-induced hypertension. Results: Renal tubular OCR data show that PT of SS rats preferred to use lactate, glutamine, and palmitate, while mTAL preferred to use glucose, pyruvate, and lactate for ATP production under LS diet condition. HS diet resulted in significantly reduced substrate-induced OCR in PT but increased OCR in mTAL. In addition, HS induced a higher level of OCR in the baseline as well as when oligomycin (an inhibitor of F1F0-ATP synthase) was added to both PT and mTAL suspensions indicating that an increased proton leakage/uncoupling of mitochondria occurs in SS rats during the development of salt-induced hypertension. Conclusion: Our emergent data demonstrated that the mitochondrial respiratory function is differentially altered in the PT and mTAL of SS rats in response to different circulatory substrates during the development of salt-induced hypertension. These changes in metabolism appear to be necessary to meet the increased tubular workloads and need for greater ATP production and O2 utilization in both the PT and mTAL of SS rats. NIH R01-HL151587. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"96 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73585954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective alpha 1-adrenergic blockade attenuates resting beat-to-beat blood pressure variability in healthy young men","authors":"L. Vianna, Gustavo Rodrigues, M. Daher, A. Teixeira, Igor Fernandes","doi":"10.1152/physiol.2023.38.s1.5732317","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5732317","url":null,"abstract":"Resting beat-to-beat blood pressure variability is a powerful predictor of cardiovascular events and end-organ damage. However, its underlying mechanisms remain incompletely understood. For instance, alterations in beat-to-beat blood pressure variability are thought to be driven by changes in both the reflex control of the autonomic nervous system and peripheral vascular function. To determine the role of peripheral sympathetic vasoconstriction on the beat-to-beat blood pressure variability, beat-to-beat heart rate (HR, by electrocardiography) and blood pressure (finger photoplethysmography) were continuously measured in seven healthy men (22 ± 5 yr) at rest (supine position), with and without (Control) a systemic and selective blockade of alpha 1-adrenergic receptors through the oral administration of Prazosin (1 mg/20 kg of body weight). Stroke volume was estimated from the blood pressure waveform (ModelFlow), permitting the calculation of cardiac output and total peripheral resistance. Two hours post-Prazosin ingestion, blood pressure responses to intravenous bolus infusion of phenylephrine were robustly reduced (-80 ± 15%, P = 0.001), indicating a significant functional blockade of alpha 1-adrenergic receptors. However, all resting hemodynamic variables were unchanged after the oral ingestion of Prazosin. Compared with control, Prazosin significantly reduced the standard deviation of systolic (5.5 ± 0.9 vs. 3.7 ± 0.7 mmHg, P = 0.004), diastolic (3.3 ± 1.0 vs. 2.4 ± 0.6 mmHg, P = 0.05), and mean blood pressure (3.7 ± 0.8 vs. 2.5 ± 0.5 mmHg, P = 0.02), as well as cardiac output (652 ± 251 vs. 428 ± 78 mL/min, P = 0.02) and total peripheral resistance (1.1 ± 0.6 vs. 0.5 ± 0.4 mmHg/L/min, P = 0.03). Similar results were found using different indices of blood pressure variability. Altogether, these findings suggest that peripheral sympathetic vasoconstriction plays a pivotal role in modulating resting beat-to-beat blood pressure variability in healthy young men. National Council for Scientific and Technological Development (CNPq; grant: 307293/2019-0 and 431740/2018-6). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"41 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72700476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optogenetic therapy on cardiac vagal dysfunction-related ventricular arrhythmia in type 2 diabetes","authors":"Wenfeng Hu, H. Tu, M. Wadman, Yulong Li, Dongze Zhang","doi":"10.1152/physiol.2023.38.s1.5727980","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5727980","url":null,"abstract":"Withdrawal of cardiac vagal activity is associated with ventricular arrhythmias-related sudden cardiac death and high mortality in T2DM patients. Although vagal nerve stimulation (VNS) has emerged as a promising therapy for ventricular arrhythmias, VNS-induced off-target side effects due to a lack of organ specificity severely limit its prescription in the clinic. To avoid the limitations of the VNS, we employed an optogenetic technique that combines with a miniaturized bio-optoelectronic implant with genetic targeting strategies to achieve cardiac-specific vagal activation in T2DM rats. We hypothesize that optogenetic activation in cardiac vagal postganglionic (CVP) neurons can restore vagal control of cardiac function, and further reduce susceptibility to ventricular arrhythmias in T2DM. Rat T2DM was induced by a high-fat diet plus streptozotocin injection. AAV-channelrhodopsin-2 (ChR2, 2 μl, 5x1012 vg/ml), an excitatory light-sensitive opsin gene, was in vivo transfected into CVP neurons located in the atrioventricular ganglion (AVG). At three weeks after opsin gene (i.e., AAV-ChR2) transfection, continual optogenetic stimulation in CVP neurons was applied twice daily (10 Hz, 50% duty cycle, 5 mW for 1 hour) by illuminating a LED probe that is controlled and powered wirelessly in conscious rats. Our data from immunofluorescence staining showed that microinjection of AAV-ChR2 into the AVG induced expression of ChR2-mcherry in almost all CVP neurons. Optogenetic activation of CVP neurons resulted in a negative inotropic reaction on the left ventricular systolic pressure in a frequency-dependent manner in anesthetized rats. Data from spectral analysis of heart rate variability demonstrated that optogenetic stimulation gradually restored T2DM-reduced high-frequency power (an index of cardiac vagal activation) from one to three days after optogenetic therapy in vivo, whereas it has no effect on low-frequency power (an index of cardiac sympathetic activation). Additionally, data from 24-hour continuous ECG recording in conscious rats demonstrated that optogenetic stimulation in CVP neurons improved the T2DM-impaired heterogeneity of ventricular electrical activity, which was measured by evaluating ventricular arrhythmia-related ECG parameters at three days after optogenetic therapy in vivo. These data suggested that optogenetic activation in CVP neurons might be an effective intervention against cardiac vagal dysfunction-related ventricular arrhythmias in the T2DM state. This study was supported by the Great Plains IDeA-CTR Pilot Grant (to DZ), NIH-NHLBI (R01HL144146 to YLL), and AHA Career Development Award (851929 to DZ). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"97 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72770361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism-insulin secretion coupling in pancreatic beta-cells: the protective role of urolithin B towards IAPP aggregation, insulin release and mitochondrial respiration","authors":"Luis Monteiro Rodrigues, Sofia Ferreira, A. Raimundo, V. Pobre, M. Garcez, Mafalda da Silva, Jose Brito, Daniel J. V. A. dos Santos, N. Saraiva, Catarina C. F. Homem, Claudia dos Santos, Regina Echaniz","doi":"10.1152/physiol.2023.38.s1.5790088","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5790088","url":null,"abstract":"Intracellular aggregation and pancreatic deposition of Islet Amyloid Polypeptide (IAPP, or amylin) is an important trigger of β-cell dysfunction in type 2 diabetes and prevention of this process represents an attractive strategy to improve β-cell functionality. (Poly)phenols, particularly small molecule polyphenol metabolites (SMPMs) resulting from the metabolism by the colonic microbiota, have emerged as promising lead molecules.This study aimed to identify SMPMs inhibiting IAPP aggregation and to elucidate their activity towards the improvement of β-cell function. Docking analyzes revealed urolithin B (UroB) as the SMPM with the highest potential to interact with IAPP. In cell-free assays, UroB modulated the aggregation kinetics of IAPP fibril formation probably due to its accommodation in the hydrophobic pocket of IAPP monomer. The cytoprotective effects of UroB were then investigated in INS-1 832/3 pancreatic β-cells challenged with in vitro pre-formed IAPP aggregates. The pre-treatment of cells with 50 μM urolithin B for 12 h ameliorated IAPP-impaired cell viability and improved redox homeostasis and membrane integrity. Transcriptomic analysis pointed out Ca2+-signaling, and insulin secretion as top molecular pathways enriched in IAPP-exposed cells treated with UroB compared to the untreated control. Corroborating this, UroB protected against Ca2+ imbalance and mitochondrial dysregulation, resulting in improved glucose stimulated insulin secretion. Monitoring of oxygen consumption rate showed that UroB restored the mitochondrial respiration function in cells damaged by IAPP aggregates. Particularly, UroB re-established the energetic demand of the cells under baseline conditions, restored the ATP levels produced by the mitochondria, and rescued the spare respiratory capacity of cells subjected to IAPP insult. These effects translate into an increased capacity of cells to respond to energetic demands and, consequently, an improved cell fitness.Overall, our data revealed that UroB inhibits IAPP aggregation and modulates diverse cellular mechanisms assisting β-cells to deal with IAPP damage. This study discloses a novel set of molecules, the SMPMs, with the potential to prevent IAPP proteotoxicity and to promote metabolic homeostasis. This research is funded by Fundação Ciência Tecnologia (FCT) by grant UIDB/04567/2020. R. Menezes is supported by the Science Employment Stimulus program from FCT. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"342 3","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72388492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Addressing underrepresentation in physiology research through internship opportunities","authors":"Vincent Barnett, Steven Wu, Joseph Metzger, L. Anderson","doi":"10.1152/physiol.2023.38.s1.5735290","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5735290","url":null,"abstract":"A challenge in the undergraduate physiology landscape is that some students who are underrepresented in the biomedical sciences are not aware of or are unable to take advantage of laboratory research opportunities. This is unfortunate because lab research can provide students with unique skill sets that are beneficial for future success, whether the students remain in research or move on to other careers. These skills include opportunities for critical thinking, improvement of oral and written communication skills, development of teamwork and leadership skills, learning about ethics in biomedical decision making and enhancement of digital literacy among others. As a program that sponsors an undergraduate Human Physiology major that has been successful in attracting underrepresented students (>40% students of color and >60% female) for a major Land-grant university, we challenged ourselves to consider how we might help our students make the most of their physiological interests and potentially improve the demographics of representation in our discipline. Starting in the summer of 2020, a group of faculty began a series of meetings to define an undergraduate program that would attract underrepresented students to lab-based internships, minimize the need for outside work by providing stipends and nurture their academic progress through informal student-faculty interactions. Though delayed by the Covid-19 pandemic, this framework has been used to initiate two new outreach programs. In the summer of 2021, we used this framework to initiate an American Heart Association sponsored research internship opportunity for 3rd and 4th year students. This program which we have named UPRIME is the focus of another abstract at this meeting. The INPUT (INtegrative biology and Physiology Undergraduate Training) program was started in fall of 2022. The program is internally supported and targets 1st and 2nd year undergraduates who represent populations that have been underrepresented in biomedical sciences. These students will be provided laboratory research experiences coupled with opportunities for educational support. A stipend of $3000 per student per semester is offered with the prospect of renewal dependent on a post-semester review. A cohort of six students were selected from a campus wide solicitation for applications into the inaugural INPUT class. These students will begin their projects in January 2023. We look forward to contributing to the scientific growth and development of these students. Perceptions of lab-based research and academic progress will be tracked along with career aspirations as the program progresses. Department of Integrative Biology and Physiology, University of Minnesota Medical School This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review ","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"9 4","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72493048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sympathetic transduction to blood pressure at rest is maintained in heart failure with preserved ejection fraction","authors":"S. Hissen, Ryosuke Takeda, Takuro Washio, John D Akins, C. Hearon, J. MacNamara, S. Sarma, B. Levine, P. Fadel, Qi Fu","doi":"10.1152/physiol.2023.38.s1.5731148","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5731148","url":null,"abstract":"Introduction: The transduction of sympathetic vasoconstrictor drive to blood pressure (BP) at rest is blunted in patients with hypertension and heart failure with reduced ejection fraction. Whether this is the case in patients with heart failure with preserved ejection fraction (HFpEF), who have a high prevalence of hypertension, remains unknown. Furthermore, it is unclear whether the two established methods used to quantify sympathetic transduction at rest provide complementary information in patient populations. Therefore, the aim of this study was to comprehensively evaluate sympathetic transduction at rest in patients with HFpEF. We hypothesized that sympathetic transduction is blunted in patients with HFpEF compared to age-matched controls. Furthermore, we hypothesized that blunted sympathetic transduction in patients with HFpEF would be observed using both signal averaging and linear regression slope analyses techniques. Methods: BP, heart rate and muscle sympathetic nerve activity (MSNA, microneurography) were measured in 25 patients with HFpEF (70±8 (SD) years, 17 females) and 41 age-matched controls (70±6 years, 25 female; hypertension prevalence 66%) during 7-10 minutes of supine rest. In a subgroup, sympathetic transduction to diastolic BP in 13 HFpEF and 15 controls was evaluated using two analytical techniques: 1) signal averaging the beat-to-beat changes in diastolic BP following bursts of MSNA, with the peak change representing sympathetic transduction; and 2) the slope of the linear relationship between diastolic BP and MSNA burst area summed across a two cardiac cycle window at a fixed lag of 6-8 cardiac cycles preceding each diastolic BP. Results: Patients with HFpEF had similar resting BP (systolic 130±26 vs. 126±16 mmHg, P=0.89; diastolic 71±15 vs. 72±10 mmHg, P=0.64), greater heart rate (70±10 vs. 62±7 bpm, P<0.001) and a trend for greater MSNA burst frequency (39±15 vs. 32±12 bursts/min, P=0.06) but similar levels of MSNA burst incidence (55±20 vs. 51±20 bursts/100heartbeats, P=0.42) when compared with controls. In the subgroup, sympathetic transduction was comparable between HFpEF and controls when evaluated using both the signal averaging (Δ0.8±0.6 vs. Δ1±0.7 mmHg, P=0.45) and the linear regression slope (0.07±0.07 vs. 0.07±0.08 mmHg/%.s, P=0.33) methods. There was a moderate positive linear relationship between methods (r2=0.39, P<0.001). Conclusion: Contrary to our hypothesis, these preliminary findings suggest that sympathetic transduction to BP at rest is preserved in patients with HFpEF compared with age-matched hypertensive controls. Furthermore, the signal averaging and linear regression slope analyses approaches provide complementary information on resting sympathetic transduction in patients with HFpEF and age-matched controls. Whether sympathetic transduction to BP in response to physiological stressors is also altered in HFpEF remains to be determined. Supported by the National Institute of Health (P01HL137630 a","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"57 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72820822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What really matters mobility of middle-aged and older adults: low muscle mass or obesity?","authors":"Chiao-Nan Chen, Kuo-Jen Hsu, Shu-Chen Chen, Kuei-Yu Chien","doi":"10.1152/physiol.2023.38.s1.5730639","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5730639","url":null,"abstract":"Study objective: This study explored which body size–adjusted skeletal muscle indices (SMI) has a better correlation with mobility and cardiometabolic health. Additionally, the roles of low muscle mass and obesity in the mobility and cardiometabolic health of individuals were identified. We hypothesized that body mass index (BMI)-or body weight (Wt)-adjusted SMI had a better correlation with mobility in middle-aged and older adults with obesity than did body height (Ht)-adjusted SMI. Methods: 427 community-dwelling middle-aged and older adults (age: 66.0±9.0 years) underwent assessments of body composition (dual-energy X-ray absorptiometry and waist circumference [WC]), grip strength, and mobility (timed up-and-go test and chair stand test). WC was used as a surrogate for obesity. Chi-square test and one-way analysis of variance were used to compare grip strength, mobility, and cardiometabolic health among individuals with normal body composition (N), only low muscle mass (S), only obesity (O), and low muscle mass plus obesity (SO). Pearson’s correlation coefficient was used to examine the correlation between muscle strength/mobility and different body size–adjusted SMI. Regression models were used to examine the factors independently associated with muscle strength, mobility, and cardiometabolic health. The significance level was set at α<0.05. Results: The O group, but not the S group, had poorer mobility than the N group, regardless of the SMI used to define low muscle mass. The O and SO groups had a higher prevalence of cardiometabolic diseases. The relationship between muscle mass and mobility existed in individuals with obesity, but not in individuals without obesity. After adjusting for age, sex, and WC, ASM/BMI was the only SMI that was correlated with grip strength. Similarly, only ASM/BMI was positively correlated with performance on the timed up-and-go test in the population with obesity (p<0.05). When age and sex were controlled, WC, but not SMI (regardless of adjusting for Ht, Wt, or BMI), was associated with mobility and cardiometabolic health. Conclusion: BMI-adjusted SMI had a better correlation with mobility in middle-aged and older adults with obesity than did Ht- and Wt-adjusted SMI. Obesity plays a more independent role in mobility and cardiometabolic health than low muscle mass in middle-aged and older adults. This study was supported by the Ministry of Science and Technology, Taiwan This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"40 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74556325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in arterial stiffness and sympathetic activity in older CKD patients","authors":"M. Zanuzzi, Jinhee Jeong, Dana Dacosta, Jeanie Park","doi":"10.1152/physiol.2023.38.s1.5785895","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5785895","url":null,"abstract":"Chronic kidney disease (CKD) is characterized by sympathetic nervous system overactivity that contributes to increased arterial stiffness and cardiovascular risk. While premenopausal females are relatively protected from cardiovascular disease in healthy individuals, older postmenopausal females without kidney disease have similar degrees of sympathetic overactivity, vascular stiffness and cardiovascular risk compared to older age-matched males in the general population. However, in the CKD population, cardiovascular mortality risk remains higher in older males compared to age-matched females and whether sex differences in neural and vascular function exist in older CKD patients is unknown. Therefore, we tested the hypothesis that compared to older females, older males with CKD have higher baseline sympathetic activity that is related to increased arterial stiffness. In 207 CKD patients (N=90 females, 62 ± 9 years; and N=117 males, 60 ± 9 years), we measured resting sympathetic nerve activity directed to muscle (MSNA) by microneurography at the peroneal nerve. At a separate visit, arterial stiffness was determined by carotid-to-femoral pulse wave velocity (PWV) using transcutaneous Doppler flow velocity (SphygmoCor®). Office blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM; Spacelabs) were performed using standard techniques. Resting MSNA was higher in males versus females with CKD (43 ± 10 vs 31 ± 14 bursts/min; p= 0.039). Both office and 24-hour ambulatory diastolic BP (79 ± 11 vs 67 ± 14 mmHg, p<0.001) and mean arterial pressure (96 ± 10 vs 88 ± 13 mmHg, p<0.001) were also higher in males versus females. PWV was not different between male and female groups (p= 0.157). There was no association between PWV and resting MSNA in males, while in females, there was an inverse relationship between PWV and MSNA burst frequency (r2=0.271; p=0.039) and burst incidence (r2=0.310; p=0.025). Older male CKD patients have higher resting MSNA, office and ambulatory BP compared to older females with CKD. In contrast, there were no differences in arterial stiffness measured as PWV between sexes. In males, increased MSNA was not associated with increased arterial stiffness, while MSNA was negatively correlated with PWV in females. Sex differences in neural and vascular function may impact cardiovascular outcomes in older patients with CKD. Supported by NIH grants R01HL135183, R33AT010457. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"109 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74570103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periodontitis accelerates the development of arterial hypertension in spontaneously hypertensive rats (SHR)","authors":"T. Buzinari, J. Castania, S. Salvador, H. Salgado","doi":"10.1152/physiol.2023.38.s1.5729825","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5729825","url":null,"abstract":"Objectives: Arterial hypertension and the inflammatory process are pathophysiologically associated. Of note, it is well understood that periodontitis is an inflammatory morbidity, epidemiologically related to cardiovascular mortality, particularly with the risk of developing arterial hypertension. Considering that in Spontaneously Hypertensive Rats (SHR) the elevation of arterial pressure starts from the 7th week of age, this study aimed to evaluate whether periodontitis accelerates the onset of arterial hypertension, for instance, in 5-week-old SHR. Methods: Induction of periodontitis was started in 3-week-old SHR and maintained for 2 weeks through the ligation of the left first molar with a silk suture, followed by the Porphyromonas gingivalis (strain W83) administration, p.o., 3 times a week. The femoral artery of 5-week-old SHR was cannulated, and 24 hours later, with the animals awakened, the systolic (SAP), diastolic (DAP), and mean (MAP) arterial pressures were recorded. Results: 5-week-old control SHR (SHAM) did not have installed arterial hypertension, while SHR with periodontitis (PER) exhibited a higher arterial pressure when compared to the SHAM group (SAP PER: 150±4 vs. SAP SHAM: 124±3 mmHg, n=8, p≤0.001; DAP PER: 103±5 vs. DAP SHAM: 85±5 mmHg, n=8, p≤0.05; MAP PER: 119±4 vs. MAP SHAM 98±4 mmHg n=8, p ≤0.01). Conclusion: The differences observed in the pressure values between the groups studied demonstrate that periodontitis accelerates the development of hypertension in SHR. Funding Sources: Fundação de Amparo à Pesquisa do Estados de São Paulo - FAPESP, Process 2021/08622-7 and 2020/06043-7. Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq, Process 306994/2021-6 and 423999/2021-4. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"53 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74667329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Potential of Extracellular Vesicles to Restore Alcohol-mediated Impairment of Myoblast Differentiation","authors":"L. Simon, B. Bourgeois, P. Molina","doi":"10.1152/physiol.2023.38.s1.5734763","DOIUrl":"https://doi.org/10.1152/physiol.2023.38.s1.5734763","url":null,"abstract":"At-risk alcohol use in people living with HIV (PLWH) and chronic binge alcohol (CBA) administration in simian immunodeficiency virus (SIV)-infected macaques are associated with dysfunctional skeletal muscle mass. Our studies have shown that decreased myomiR-206 expression in skeletal muscle and myoblasts isolated from CBA/SIV macaques contributes to decreased myoblast differentiation. miRs transported in extracellular vesicles (EVs) mediate numerous cellular responses through intercellular communication. This study tested the hypothesis that delivery of miR-206 in EVs would ameliorate CBA-mediated decreased myoblast differentiation. Eight female rhesus macaques received either (CBA, 2.5g/kg/day) or water (VEH) for 14.5 months. Three months following the initiation of CBA/VEH, animals were infected with SIVmac251 and initiated on antiretroviral therapy 2.5 months later. Myoblasts were isolated from the vastus lateralis muscle at study endpoint (blood alcohol concentration= 0 mM) from each animal and used for ex vivo experiments including measuring differentiation, transfecting with a miR-206 mimic, and isolating EVs from myotube culture supernatant via ultracentrifugation. Myoblast differentiation measured by fusion index was lower in CBA myotubes compared to VEH (p<0.05). CBA decreased myotube-derived EV miR-206 expression (p<0.01). Transfection of myoblasts isolated from the CBA group with a mir-206 mimic increased myotube fusion index (p<0.05). Moreover, delivery of exogenous miR-206 in plasma-derived EVs increased myotube expression of miR-206 by over 450-fold (p<0.001) and significantly improved myoblast differentiation as measured by fusion index and myotube density (p<0.05). These results provide evidence that delivering miR-206 through EVs can increase CBA-mediated SKM stem cell differentiation. We propose these findings support the possible use of autologous plasma EVs as therapeutical vehicles devoid of the known adverse effects of synthetic cargo nanocarriers. Supported by: NIH/NIAAA P60AA009803, F30AA029358, K01AA024494. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.","PeriodicalId":49694,"journal":{"name":"Physiology","volume":"94 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77501012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}