Pflugers Archiv : European journal of physiology最新文献

{"title":"Impact of combined exercise training in peripheral and diaphragm muscles and in mortality in a preclinical model of pulmonary arterial hypertension.","authors":"Thais C Freire, Antônio V Nascimento-Filho, Marília S Ferreira, Danielle da Silva Dias, Victor Miranda, Marina Dutra, Larissa Seibt, Andrey Serra, Denielli da Silva Gonçalves Bos, Maria Cláudia Irigoyen, Marcelle Paula-Ribeiro, Kátia De Angelis","doi":"10.1007/s00424-025-03118-z","DOIUrl":"https://doi.org/10.1007/s00424-025-03118-z","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a progressive disease characterised by systemic oxidative stress and inflammation that extends beyond the pulmonary vasculature to the musculoskeletal system. Combined exercise training (ET), incorporating aerobic and resistance components, is a promising non-pharmacological intervention, but its effects on musculoskeletal oxidative stress and inflammation remain unclear. To evaluate the effects of combined ET on musculoskeletal oxidative stress and inflammation, muscle wasting, and survival in a monocrotaline (MCT)-induced PAH. Male Wistar rats were assigned to MCT-treated sedentary (MCT-SED) or ET (MCT-ET) groups (n = 12/group), or saline-treated sedentary (SAL-SED) or ET (SAL-ET) controls (n = 8/group). PAH was induced via MCT injection (MCT, 40 mg/kg). The ET consisted of moderate-intensity interval aerobic (3x/week) and resistance (2x/week) training for four weeks. Muscle mass, oxidative stress and inflammation markers (IL-6, IL-10, TNF-α) were assessed in gastrocnemius and diaphragm muscles. PAH increased oxidative damage, reduced antioxidant defences, and elevated inflammatory markers in both muscles, contributing to muscle loss. Combined ET enhanced gastrocnemius antioxidant capacity (FRAP, SOD), reduced pro-oxidants (hydrogen peroxide, nitrite), and attenuated oxidative damage (TBARS, carbonyls) in both muscles. Combined ET decreased pro-inflammatory markers (IL-6, TNF-α), prevented diaphragm atrophy, and improved survival (MCT-SED vs. MCT-ET, p = 0.03; hazard ratio, 4.3; 95% CI, 1.2-15.1). Combined interval ET improved redox balance and inflammatory profiles in both peripheral and respiratory muscles. These adaptations were linked to reduced diaphragm muscle wasting and enhanced survival in MCT-induced PAH. Our findings support combined ET as a non-pharmacological strategy for managing systemic complications of PAH.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080341","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}

{"title":"Effects of intrarenal afferent stimulation by bradykinin on renal sympathetic nerve activity: tonic inhibition contributing to renal function.","authors":"Eva Hutter, Tilmann Ditting, Martin Hindermann, Karl F Hilgers, Roland E Schmieder, Christian Morath, Mario Schiffer, Kerstin Amann, Roland Veelken, Kristina Rodionova","doi":"10.1007/s00424-025-03116-1","DOIUrl":"https://doi.org/10.1007/s00424-025-03116-1","url":null,"abstract":"<p><p>Bradykinin (BK) may increase renal sodium excretion by decreasing tubular ENaC activity. Afferent renal nerve activity (ARNA) putatively controls renal sympathetic nerve activity (RSNA) involved in renal sodium handling. We recently found tonic sympatho-inhibition due to intrarenal ARNA stimulation by the TRPV1 agonist capsaicin (CAP). Since BK is known to augment TRPV1 effects, we hypothesized that intrarenally applied BK also tonically inhibits RSNA. Four groups of rats (n = 8; BK, CAP, HOE + BK, NaCl-control) were equipped with arterial and venous catheters for blood pressure (BP) and heart rate (HR) recordings and drug application; bipolar electrodes for RSNA and ARNA recordings, renal arterial catheter for intrarenal administration (IRA) of bradykinin (BK: 10^-5 M, 20 µl and 10^-4 M; 2.5, 5, 10 µl), capsaicin (CAP 3.3, 6.6, 10 and 33*10^-7 M, 10 µl). The B2-receptor antagonist HOE-140 (10^-4 M, 40 µl) was administered intravenously (IV) just before IRA BK (HOE + BK), finally the NK₁-receptor blocker RP67580 (10^-2 M, 15 µl; IV) was applied in all groups at the end of the experiment. IRA BK and CAP momentarily increased ARNA. IRA CAP, IRA BK, and IRA HOE + BK, decreased RSNA from 4.2 ± 0.8 to 1.3 ± 0.2 µV*sec (BK, P < 0.01), 3.6 ± 0.5 to 0.9 ± 0.2 µV*sec (CAP, P < 0.01) and 3.2 ± 0.3 to 0.8 ± 0.1 µV*sec (HOE-BK, P < 0.01). Suppressed RSNA (BK, CAP, HOE + BK) was unmasked by IV RP67580: 1.6 ± 0.5 to 8.6 ± 2.9 µV*sec (BK, P < 0.01); 1.0 ± 0.2 to 6.1 ± 1.5 µV*sec (CAP, P < 0.01); 0.8 ± 0.2 to 4.5 ± 0.8 µV*sec (HOE-BK, P < 0.05). IRA BK was associated with momentary increases of RSNA, abolished by HOE-140. Intrarenal stimulation of renal afferent nerves by BK induced tonic renal sympathodepression likely augmenting sodium and water excretion.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145033992","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}

{"title":"Comment on \"spatially dependent tissue distribution of thyroid hormones by plasma thyroid hormone binding proteins\".","authors":"Amnuay Kleebayoon, Viroj Wiwanitkit","doi":"10.1007/s00424-025-03111-6","DOIUrl":"https://doi.org/10.1007/s00424-025-03111-6","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030236","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}

{"title":"Pregnancy induces intestinal epithelial elongation and estriol-associated activation of the Hippo signaling pathway in a mouse model.","authors":"Niklas Fritz Gängler, Cathrine Knoblauch, Franziska Hill, Bastian Lukas Zeeb, Maren Falk-Paulsen, Philip Rosenstiel, Laura Katharina Sievers","doi":"10.1007/s00424-025-03107-2","DOIUrl":"10.1007/s00424-025-03107-2","url":null,"abstract":"<p><p>During pregnancy and weaning, the intestinal tract undergoes adaptations on different levels, including altered immune cell frequencies and epithelial changes. We could show in a mouse model that the overall area (crypt-villus axis length and total length) of the small intestine increased during this period of higher maternal nutrient need and that the increased area correlated with maternal weight. Quantification of cell proliferation and cell death showed an increased proliferation of epithelial cells in the lower and middle crypt. In cell culture, estriol maintained epithelial cell proliferation and progesterone-inhibited proliferation. Further, Hippo signaling is a well-known pro-proliferative pathway which integrates several upstream signals and ultimately leads to nuclear translocation of the transcription factor YAP. In the small intestine, YAP is expressed in epithelial cells, immune cells, and fibroblasts. During pregnancy and weaning, epithelial and stroma cells exhibit strong nuclear staining of YAP. Interestingly, estriol led to upregulation and increased nuclear shuttling of YAP in intestinal epithelial cell monolayers. This effect appears to be specific to the estriol treatment since the established pro-proliferative cytokine GLP-2 did not lead to increased nuclear shuttling of YAP.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1201-1212"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Christian Bauer-physiologist, mentor, and philosopher.","authors":"Armin Kurtz, Kai-Uwe Eckardt, Max Gassmann, Hugo Marti, Josef Pfeilschifter, Holger Scholz, Roland Wenger","doi":"10.1007/s00424-025-03109-0","DOIUrl":"10.1007/s00424-025-03109-0","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1131-1134"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the quantification of post-occlusive reactive hyperemia: a multimodal optical approach.","authors":"Henrique Silva, Carlota Rezendes, Pedro Contreiras Pinto","doi":"10.1007/s00424-025-03110-7","DOIUrl":"10.1007/s00424-025-03110-7","url":null,"abstract":"<p><p>Post-occlusive reactive hyperemia (PORH) is a physiological response marked by a transient increase in microvascular perfusion following ischemia. While cutaneous perfusion during PORH has been extensively characterized using optical approaches such as Doppler-based techniques, low-cost alternatives like photoplethysmography (PPG), videocapillaroscopy (VC) and near-infrared reflectance imaging (NIRI) may provide complementary insights into both microvascular and venous dynamics. However, their role in quantifying PORH remains underexplored. This study aimed to evaluate the potential of low-magnification VC and NIRI-based imaging for quantifying perfusion changes during a standardized PORH protocol in healthy subjects, using PPG as a reference. Fourteen participants (21.5 ± 4.2 years) underwent suprasystolic occlusion of a randomly selected upper limb, with simultaneous recordings using PPG and VC at the finger and NIRI at the dorsal hand veins. The protocol included a 5-min baseline, 3-min occlusion (200 mmHg), and 5-min recovery. Skin blood flow was derived from the PPG signal, a hemoglobin index (C_Hb) was extracted from VC images, and vein width was measured using NIRI. Nonparametric statistics were used for analysis. Arterial occlusion significantly reduced skin blood flow (-95.3%, p < 0.001) and C_Hb (-8.3%, p = 0.007), with milder contralateral changes. Vein width increased during occlusion (p = 0.003) and returned to baseline during recovery. VC was less sensitive than PPG but reproduced the expected hemodynamic profile. A positive correlation was found between venous dilation during recovery and the decrement velocity of microvascular perfusion during occlusion. VC and NIRI represent accessible and complementary tools for assessing vascular responses during PORH. Their combined application may enhance non-invasive vascular evaluation in both clinical and research settings.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1213-1224"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The machinery of healthy vasodilatation: an overview.","authors":"Jana Pourová, Patrícia Dias, Milan Pour, Přemysl Mladěnka","doi":"10.1007/s00424-025-03096-2","DOIUrl":"10.1007/s00424-025-03096-2","url":null,"abstract":"<p><p>Cardiovascular function depends on an adequate vascular tone facilitating appropriate blood flow to individual tissues according to their needs. The tone results from the interplay between vasodilatation and vasoconstriction. Its rapid and efficient regulation is secured by many interconnected physiological mechanisms, both at the level of the vascular smooth muscle and the endothelium. The purpose of this review is to provide an update of the current knowledge on the mechanisms of physiological vasodilatation. First, two principal intracellular signaling pathways linked to the activation of protein kinases PKA and PKG are introduced. Subsequently, the role of endothelium-derived relaxing factors together with the endothelium-dependent hyperpolarization is discussed. The roles of ion channels and gap junctions in the communication between endothelium and vascular smooth muscle cells are particularly discussed. Finally, principal vasodilatory stimuli (mechanical, thermal, chemical) and their mechanisms of action are briefly introduced.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1135-1162"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voltage-gated Na⁺ channels: key players in the early tumorigenesis of breast cancer.","authors":"Paula Rhana, Flávia Carvalho Aguiar, Diego Santos Souza, Ênio Ferreira Lima, Andréia Laura Prates Rodrigues, Jader Santos Cruz","doi":"10.1007/s00424-025-03106-3","DOIUrl":"10.1007/s00424-025-03106-3","url":null,"abstract":"<p><p>Voltage-gated Na⁺ channels (VGSCs) are recognized for their roles in cancer biology, particularly in promoting tumor aggressiveness. However, their presence and functional significance in early-stage breast cancer remain poorly understood. This study investigates the physiological role of VGSCs in breast cancer progression, focusing on their contribution to metastatic potential and their promise as novel therapeutic targets. To address these issues, we examined VGSCs expression and electrophysiological properties in two primary breast tumor cell lines, MACL-1 and MGSO-3, using patch-clamp whole-cell recordings. Both exhibited fast inward currents, peaking near 0 mV, which were abolished by extracellular Na⁺ removal, confirming that inward current was due to the presence of VGSCs. Pharmacological inhibition with tetrodotoxin (TTX, 100 nM) showed that MACL-1 cells exclusively express TTX-sensitive VGSCs, while MGSO-3 cells express both TTX-sensitive and -resistant VGSCs. In contrast, non-tumoral MCF-10A breast cells, although they express VGSCs, showed no detectable inward Na⁺ current. Despite having similar Na⁺ current activation properties, the Na⁺ current in MGSO-3 cells exhibited slower inactivation kinetics compared to MACL-1 cells, suggesting functional heterogeneity. However, neither TTX nor anemone toxin (ATX) influenced proliferation or migration, challenging the established link between VGSCs and tumor aggressiveness in early-stage breast cancer. Immunocytochemistry revealed the presence of Nav1.5 (a TTX-resistant VGSC isoform), Nav1.6, and Nav1.7 (TTX-sensitive VGSCs isoforms) in both non-tumoral and tumoral cells, with these isoforms localized to different intracellular compartments, raising questions about their regulatory roles.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1191-1200"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699236","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}

{"title":"Correction to: The machinery of healthy vasodilatation: an overview.","authors":"Jana Pourová, Patrícia Dias, Milan Pour, Přemysl Mladěnka","doi":"10.1007/s00424-025-03102-7","DOIUrl":"10.1007/s00424-025-03102-7","url":null,"abstract":"","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1225"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The machinery of healthy vasoconstriction: an overview.","authors":"Jana Pourová, Patrícia Dias, Milan Pour, Přemysl Mladěnka","doi":"10.1007/s00424-025-03103-6","DOIUrl":"10.1007/s00424-025-03103-6","url":null,"abstract":"<p><p>Tissue perfusion is acutely regulated by the changes in the vascular tone resulting in vasodilatation or vasoconstriction (there are also long-term changes in tissue perfusion, effectively accomplished by vascular remodeling). Even though vasodilatation predominates under physiological conditions, vasoconstriction represents an essential part of normal vascular physiology. The process of vasoconstriction is very complex, being influenced by many mediators, some of which are produced by the adjacent endothelial cells. The purpose of this review is to provide an overview of the machinery of vasoconstriction addressing the main components. First, the role of calcium is discussed including its intracellular and extracellular sources, its principal function in smooth muscle contraction machinery and mechanisms counteracting its effects. Subsequently, protein kinase C is included with its activation, effects and feedback. The role of RhoA/ROCK system is addressed in a similar way. The next section deals with the role of vascular endothelium-derived contracting factors and their effects on the adjacent smooth muscle cells. Finally, principal mechanisms of action of vasoconstrictive stimuli and myogenic tone are concisely discussed.</p>","PeriodicalId":19954,"journal":{"name":"Pflugers Archiv : European journal of physiology","volume":" ","pages":"1163-1189"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144609031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}