Canadian journal of physiology and pharmacology最新文献

Nox4 Mediates Diastolic Function in a Genetic Model of Pitx2 Haploinsufficiency. Nox4介导Pitx2单倍不全基因模型中的舒张功能。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-10-14 DOI: 10.1139/cjpp-2026-0223

Sumner L Gardner, Anam Fatima, Faris Abusharkh, Elizabeth Kobeck, Chitra Basu, Francis J Miller, Vineet Agrawal

{"title":"Nox4 Mediates Diastolic Function in a Genetic Model of Pitx2 Haploinsufficiency.","authors":"Sumner L Gardner, Anam Fatima, Faris Abusharkh, Elizabeth Kobeck, Chitra Basu, Francis J Miller, Vineet Agrawal","doi":"10.1139/cjpp-2026-0223","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0223","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) commonly coexists with atrial fibrillation (AF), but shared mechanisms remain unclear. In this study, we hypothesized that Pitx2, a transcription factor located near the strongest genetic locus associated with AF in humans, increases susceptibility to HFpEF-like remodeling. We also sought to understand pathways that might be central to this increased risk. Male and female Pitx2+/- mice and wild-type littermates received 3-week subcutaneous osmotic pump infusion of saline or angiotensin II (Ang II; 500 ng/kg/min). Cardiac structure and function were assessed by echocardiography and catheterization, and functional capacity by exercise treadmill. RNA transcriptomic profiling was performed to identify candidate pathways. In a separate cohort, Ang II-treated mice were randomized to oral GKT136901 (30 mg/kg/day) or vehicle during infusion. After Ang II infusion, Pitx2+/- mice developed exaggerated HFpEF-like changes, including greater left ventricular hypertrophy, left atrial enlargement, diastolic dysfunction, elevated left ventricular end-diastolic pressure, and reduced treadmill performance. RNA-seq showed enrichment of metabolic and stress-response pathways with selective upregulation of Nox4, confirmed by RT-qPCR. GKT136901 attenuated structural remodeling, diastolic dysfunction indices, elevated filling pressures, and cardiomyocyte hypertrophy, but did not improve endurance. These findings implicate redox signaling, including Nox4, in AF genetic susceptibility-HFpEF interactions.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bile Acids as Mitochondrial Toxins: Emerging Insights in Fontan and Heart Failure with Preserved Ejection Fraction. 胆汁酸作为线粒体毒素：对保留射血分数的Fontan和心力衰竭的新见解。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-10-02 DOI: 10.1139/cjpp-2026-0103

Ashish H Shah, Moreshwar S Desai

{"title":"Bile Acids as Mitochondrial Toxins: Emerging Insights in Fontan and Heart Failure with Preserved Ejection Fraction.","authors":"Ashish H Shah, Moreshwar S Desai","doi":"10.1139/cjpp-2026-0103","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0103","url":null,"abstract":"Elevated bile acids, particularly hydrophobic secondary species, impair mitochondrial structure and function across multiple organs. In cardiomyocytes, pathologically elevated circulating bile acids impair mitochondrial biogenesis, diminish ATP generation, disrupt calcium homeostasis, and compromise myocardial energetics. These alterations promote oxidative stress and activate mitochondrial apoptotic pathways, culminating in systolic dysfunction, diastolic impairment, and heightened arrhythmogenic risk. Parallel mitochondrial injury in liver and skeletal muscle contributes to liver fibrosis and sarcopenia. Accumulating evidence suggests that elevated circulating bile acids are not merely biochemical epiphenomena in Fontan circulation, where chronic hepatic congestion is intrinsic to the physiology, or in metabolic dysfunction-associated steatotic liver disease (MASLD). Rather, bile acid excess may represent a mechanistic link between hepatic injury and the broader, multisystem dysfunction that characterizes both conditions. This review focuses on recognizing bile acids as systemic mitochondrial toxins that share a common pathogenic pathway to two distinct clinical settings, Fontan failure and MASLD.It also highlights emerging diagnostic opportunities and supports therapies aimed at reducing bile acid toxicity or improving mitochondrial resilience to enhance outcomes in these patients.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Decoding Dietary Fat: Molecular Sensing, Brain Integration, and the Biology of Flavor. 解码膳食脂肪：分子传感、脑整合和风味生物学。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-10-02 DOI: 10.1139/cjpp-2026-0211

Khaled Ahmed Abdel-Sater

{"title":"Decoding Dietary Fat: Molecular Sensing, Brain Integration, and the Biology of Flavor.","authors":"Khaled Ahmed Abdel-Sater","doi":"10.1139/cjpp-2026-0211","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0211","url":null,"abstract":"Background and aim: Dietary fat perception influences food preference, satiety, and metabolic regulation but remains incompletely understood. This review examines current knowledge regarding receptor-mediated fat sensing, neural integration, adaptive plasticity, and their clinical implications.Methods: Evidence was collected from major biomedical databases through June 2026. Human and experimental studies addressing molecular receptors, psychophysical testing, electrophysiology, neuroimaging, genetics, and metabolic physiology were critically synthesized.Results: CD36 and GPR120 function as principal lipid sensors alongside FFAR1, GPR84, FFAR2, and TGR5. Oral lipid detection is integrated with retronasal olfactory processing, trigeminal signaling, endocrine responses, and cortical reward networks. Fat perception demonstrates remarkable adaptability through receptor regulation, inflammatory remodeling, epigenetic modification, and dietary exposure. Methodological heterogeneity remains a major limitation across psychophysical and molecular investigations.Conclusion: Evidence supports a distributed, adaptive, and metabolically regulated system of dietary fat perception rather than an isolated sensory pathway. Improved methodological standardization and multidisciplinary approaches will accelerate translation into personalized dietary interventions and metabolic therapeutics.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Autonomic Cardiovascular Dysregulation After Acute Cervical Spinal Cord Injury: Insights From Linear and Nonlinear Heart Rate Variability. 急性颈脊髓损伤后自主心血管失调：从线性和非线性心率变异性的见解。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-09-30 DOI: 10.1139/cjpp-2026-0083

Antonija Krstačić, Goran Krstačić, Vladimir Jakovljevic, Tin Krstačić

{"title":"Autonomic Cardiovascular Dysregulation After Acute Cervical Spinal Cord Injury: Insights From Linear and Nonlinear Heart Rate Variability.","authors":"Antonija Krstačić, Goran Krstačić, Vladimir Jakovljevic, Tin Krstačić","doi":"10.1139/cjpp-2026-0083","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0083","url":null,"abstract":"Background: Acute cervical spinal cord injury (cSCI) disrupts supraspinal autonomic cardiovascular control. Heart rate variability (HRV), assessed using linear and nonlinear methods, provides a sensitive index of cardiovascular autonomic regulation.Objective: To evaluate linear and nonlinear HRV parameters associated with autonomic cardiovascular dysregulation in acute cSCI.Methods: This monocentric prospective study included 500 patients with traumatic or non-traumatic acute cSCI and 200 age- and sex-matched healthy controls. All participants underwent 24-hour Holter ECG monitoring. Time- and frequency-domain indices and nonlinear metrics, including Poincaré plot analysis, entropy, detrended fluctuation analysis, and recurrence quantification analysis, were calculated. Predictive modeling used logistic regression, random forest, gradient boosting, and support vector machine algorithms with cross-validation.Results: Both cSCI groups showed significantly reduced HRV amplitude and altered autonomic cardiovascular regulation. Nonlinear indices demonstrated reduced entropy, altered fractal scaling, and decreased recurrence dynamics. Female patients showed relatively preserved nonlinear HRV parameters. Models combining linear and nonlinear features discriminated autonomic dysfunction better than models using conventional HRV metrics alone.Conclusion: Combined linear and nonlinear HRV analysis provides complementary characterization of autonomic cardiovascular dysregulation following acute cSCI.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149104580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ET B receptors contribute to synchrony between blood pressure and other peripheral circadian rhythms in the Sprague-Dawley rat. 在Sprague-Dawley大鼠中，ET B受体有助于血压和其他外周昼夜节律的同步。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-09-26 DOI: 10.1139/cjpp-2026-0189

Maria Venegas, Hiruni M Aponso, David M Pollock

{"title":"ET B receptors contribute to synchrony between blood pressure and other peripheral circadian rhythms in the Sprague-Dawley rat.","authors":"Maria Venegas, Hiruni M Aponso, David M Pollock","doi":"10.1139/cjpp-2026-0189","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0189","url":null,"abstract":"Maintaining temporal coordination of physiological function is essential for good health. To determine how the endothelin axis regulates the timing of blood pressure (BP) and key physiological rhythms, we monitored circadian rhythmicity of BP and other variables by telemetry in male and female Sprague Dawley rats with or without chronic ETB receptor blockade (A-192621). Rats were maintained under constant dark conditions to ensure a free running status of the circadian clock. Rats were divided into groups being fed either normal salt (NS) or high salt (HS) diets starting the day of release into constant darkness. After one week, a subset of rats was given A-192621 in the food for two weeks. HS diet exacerbated amplitude of mean arterial pressure (MAP) in ETB antagonist treated rats. ETB antagonism was sufficient to delay MAP rhythms either diet. There were no changes in amplitude of heart rate (HR) or body temperature resulting in desynchrony between the phases with MAP. Rats fed a HS diet without antagonist also displayed desynchrony among all peripheral rhythms. Together these data support the notion of the endothelial system regulating BP rhythms and maintaining synchrony with peripheral physiological rhythms.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardiovascular Autonomic Dysfunction in Late-Stage Lyme Disease: A Comprehensive Autonomic Assessment. 晚期莱姆病心血管自主神经功能障碍：一项全面的自主神经评估。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-09-26 DOI: 10.1139/cjpp-2026-0066

Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Vasko Zugic, Milijana Ostojic, Aleksandra Grbovic, Smiljana Stojanovic, Dragisa Radovanovic, Vladimir Jakovljevic, Milovan Bojic

{"title":"Cardiovascular Autonomic Dysfunction in Late-Stage Lyme Disease: A Comprehensive Autonomic Assessment.","authors":"Branislav Milovanovic, Nikola Markovic, Masa Petrovic, Vasko Zugic, Milijana Ostojic, Aleksandra Grbovic, Smiljana Stojanovic, Dragisa Radovanovic, Vladimir Jakovljevic, Milovan Bojic","doi":"10.1139/cjpp-2026-0066","DOIUrl":"https://doi.org/10.1139/cjpp-2026-0066","url":null,"abstract":"Lyme disease, caused by Borrelia burgdorferi sensu lato, may lead to persistent complications, including autonomic nervous system dysfunction. Although postural orthostatic tachycardia syndrome is frequently associated with orthostatic intolerance in Lyme disease, broader autonomic impairment remains insufficiently characterized. This cross-sectional study included 324 participants: 233 patients with late-stage Lyme disease and 91 healthy controls. All participants underwent cardiovascular autonomic reflex testing, beat-to-beat heart rate variability analysis, baroreflex assessment, 24-hour Holter electrocardiography, and ambulatory blood pressure monitoring. Compared with controls, patients with Lyme disease demonstrated significantly higher rates of sympathetic and parasympathetic dysfunction (p<0.05). Heart rate variability spectral parameters, including very low frequency, low frequency, and high frequency components, were significantly reduced, while baroreflex sensitivity and baroreflex effectiveness index were also impaired (p<0.05). Holter monitoring additionally revealed reduced time-domain heart rate variability parameters and an elevated low-frequency/high-frequency ratio, suggesting relative sympathetic predominance in patients with Lyme disease (p<0.05). These findings support the presence of cardiovascular autonomic dysfunction in patients with late-stage Lyme disease and highlight the importance of comprehensive autonomic evaluation in this population. Keywords: Autonomic Dysfunction; Lyme disease; Heart rate variability; Neurocardiology.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Endoplasmic reticulum stress, calcium homeostasis, and the aging heart. 内质网应激、钙稳态与心脏老化。

IF 1.3 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 Epub Date: 2025-12-04 DOI: 10.1139/cjpp-2025-0190

Izabela Quest, Marek Michalak

引用次数: 0

Ameliorative effect of roxithromycin against prostate inflammation-induced chronic pelvic pain in a preclinical model. 罗红霉素对前列腺炎引起的慢性盆腔疼痛的改善作用

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0262

Vishnu Prabha P, Prasenjit Das, Sneha Vangaveti, Vijay L Kumar

{"title":"Ameliorative effect of roxithromycin against prostate inflammation-induced chronic pelvic pain in a preclinical model.","authors":"Vishnu Prabha P, Prasenjit Das, Sneha Vangaveti, Vijay L Kumar","doi":"10.1139/cjpp-2025-0262","DOIUrl":"10.1139/cjpp-2025-0262","url":null,"abstract":"In view of the well-known anti-inflammatory property of roxithromycin, the present study was carried out to evaluate its efficacy in ameliorating prostate inflammation-induced chronic pelvic pain in rat model. Inflammation was induced by single intraprostatic injection of carrageenan where a time course study revealed a peak histology score on day 14. The efficacy study was carried out in four sets of rats, each comprising five groups, which included respective normal and experimental controls (NC, EC). The drugs (roxithromycin 5 and 20 mg/kg, diclofenac 5 mg/kg) were given daily orally and pain score and body weight were evaluated at different time intervals. The prostatic index, vascular permeability, tissue levels of TNF-α and PGE2, thiobarbituric acid reactive substances, glutathione and superoxide dismutase, histology score, and immunoreactivity of COX-2 and iNOS were evaluated on day 14. Like diclofenac, roxithromycin decreased pain score and the rats gained weight during the study period as compared to the EC group. The beneficial effect of roxithromycin was also evident from the dose-dependent restoration of markers of inflammation and oxidative stress. This study shows that by alleviating pain and suppressing inflammation and oxidative stress, roxithromycin has a potential to provide relief in prostatitis.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":"104 ","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Seismocardiographic evidence of deteriorating cardiac function among Canadian police officers: evidence from the longitudinal royal Canadian Mounted Police posttraumatic stress disorder study. 加拿大警察心功能恶化的地震心动图证据：来自加拿大皇家骑警创伤后应激障碍纵向研究的证据。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2026-0116

T A Teckchandani, J P Neary, H J Norrie, K P Flegel, K Q Maguire, G P Krätzig, R N Carleton

{"title":"Seismocardiographic evidence of deteriorating cardiac function among Canadian police officers: evidence from the longitudinal royal Canadian Mounted Police posttraumatic stress disorder study.","authors":"T A Teckchandani, J P Neary, H J Norrie, K P Flegel, K Q Maguire, G P Krätzig, R N Carleton","doi":"10.1139/cjpp-2026-0116","DOIUrl":"10.1139/cjpp-2026-0116","url":null,"abstract":"Royal Canadian Mounted Police (RCMP) frequently encounter potentially psychologically traumatic events (PPTEs) which include direct (e.g., happened to me) or indirect (e.g., part of my job) exposure to actual or threatened death, serious injury, or sexual violence, and subsequently demonstrate an increased risk of developing posttraumatic stress injuries (PTSIs). Although PTSIs include mental health disorders, physical impairments such as the development of chronic pain and cardiovascular conditions are also implicated. The current study was designed to assess for changes in cardiac function among RCMP within their first 3 years of field service. Participants (n = 96) were mostly male (71.6%), men (71.6%), White (85.6%), with a mean age of 30.22 ± 6.22 years. The current results evidenced deteriorations in cardiac function; diastolic cardiac function began to deteriorate as early as the second year of field service, with changes in systolic function occurring concurrently, or within the following year, suggesting that deteriorating cardiac function may constitute a PTSI. Incorporating best-practice cardiac rehabilitation exercise prescription guidelines tailored to the maintenance or improvement of diastolic function into existing occupational health and wellness programs may support a mechanistic role in reducing the risk of major adverse cardiac events among RCMP officers and other high-risk occupational populations.","PeriodicalId":9520,"journal":{"name":"Canadian journal of physiology and pharmacology","volume":" ","pages":"1-14"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148677484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in heart preservation techniques for transplantation: an updated review. 心脏移植保存技术的最新进展。

IF 1.8 4区医学

Canadian journal of physiology and pharmacology Pub Date : 2026-01-01 DOI: 10.1139/cjpp-2025-0397

Chananya Karunasumetta, Ienglam Lei, Paul C Tang

引用次数: 0