Eric A. Mensah, Noriko Daneshtalab, Reza Tabrizchi
{"title":"Piezo 1 机械感受器参与了雌雄达尔盐敏感高血压大鼠离体小阻力动脉血管僵化的研究","authors":"Eric A. Mensah, Noriko Daneshtalab, Reza Tabrizchi","doi":"10.1002/prp2.1227","DOIUrl":null,"url":null,"abstract":"Piezo are mechanosensitive non‐selective cation channels that are suggested to be involved in vascular development and function. The aim of our study was to determine any sex‐specific contributions of the mechanosensitive Piezo 1 channels on blood vessel wall stiffness. Composite Young modulus (CYM) was determined using pressure myograph experimental approach using third‐order mesenteric arteries (intact and denuded) from Dahl salt‐sensitive male and female normotensive and hypertensive rats (<jats:italic>n</jats:italic> = 6–8). The effects of Piezo 1 agonist (Yoda 1; 10 μM), and antagonist (GsMTx‐4; 2 μM) were studied in intact and denuded vessels. The distribution of Piezo 1 was identified using immunohistochemistry. In intact blood vessels, there were no differences in CYM between the experimental groups, however, removal of the endothelium unmasked significant increases in CYM in normotensive males and female groups compared to hypertensive males. The presence of Yoda 1 did not affect CYM in any groups. In the intact tissues, GsMTx‐4 led to significant increases in CYM in hypertensive females, and normotensive males and females, but not in hypertensive males. In the denuded vessels, GsMTx‐4, produced a significant increase in CYM but only in the female normotensives. Differential expression of Piezo 1 were found in male versus female blood vessels. Our findings support a greater contribution of Piezo 1 mechanoceptors to vascular biomechanics of male hypertensive compared to male normotensive or female groups. The evidence also points to a possible differential vasoregulatory role for Piezo 1 in endothelial versus vascular smooth cells, with a greater contribution in males than females.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Involvement of Piezo 1 mechanoceptors in vascular stiffness in isolated small resistance arteries of male and female Dahl salt‐sensitive hypertensive rats\",\"authors\":\"Eric A. Mensah, Noriko Daneshtalab, Reza Tabrizchi\",\"doi\":\"10.1002/prp2.1227\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Piezo are mechanosensitive non‐selective cation channels that are suggested to be involved in vascular development and function. The aim of our study was to determine any sex‐specific contributions of the mechanosensitive Piezo 1 channels on blood vessel wall stiffness. Composite Young modulus (CYM) was determined using pressure myograph experimental approach using third‐order mesenteric arteries (intact and denuded) from Dahl salt‐sensitive male and female normotensive and hypertensive rats (<jats:italic>n</jats:italic> = 6–8). The effects of Piezo 1 agonist (Yoda 1; 10 μM), and antagonist (GsMTx‐4; 2 μM) were studied in intact and denuded vessels. The distribution of Piezo 1 was identified using immunohistochemistry. In intact blood vessels, there were no differences in CYM between the experimental groups, however, removal of the endothelium unmasked significant increases in CYM in normotensive males and female groups compared to hypertensive males. The presence of Yoda 1 did not affect CYM in any groups. In the intact tissues, GsMTx‐4 led to significant increases in CYM in hypertensive females, and normotensive males and females, but not in hypertensive males. In the denuded vessels, GsMTx‐4, produced a significant increase in CYM but only in the female normotensives. Differential expression of Piezo 1 were found in male versus female blood vessels. Our findings support a greater contribution of Piezo 1 mechanoceptors to vascular biomechanics of male hypertensive compared to male normotensive or female groups. The evidence also points to a possible differential vasoregulatory role for Piezo 1 in endothelial versus vascular smooth cells, with a greater contribution in males than females.\",\"PeriodicalId\":19948,\"journal\":{\"name\":\"Pharmacology Research & Perspectives\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-06-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pharmacology Research & Perspectives\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/prp2.1227\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology Research & Perspectives","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/prp2.1227","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Involvement of Piezo 1 mechanoceptors in vascular stiffness in isolated small resistance arteries of male and female Dahl salt‐sensitive hypertensive rats
Piezo are mechanosensitive non‐selective cation channels that are suggested to be involved in vascular development and function. The aim of our study was to determine any sex‐specific contributions of the mechanosensitive Piezo 1 channels on blood vessel wall stiffness. Composite Young modulus (CYM) was determined using pressure myograph experimental approach using third‐order mesenteric arteries (intact and denuded) from Dahl salt‐sensitive male and female normotensive and hypertensive rats (n = 6–8). The effects of Piezo 1 agonist (Yoda 1; 10 μM), and antagonist (GsMTx‐4; 2 μM) were studied in intact and denuded vessels. The distribution of Piezo 1 was identified using immunohistochemistry. In intact blood vessels, there were no differences in CYM between the experimental groups, however, removal of the endothelium unmasked significant increases in CYM in normotensive males and female groups compared to hypertensive males. The presence of Yoda 1 did not affect CYM in any groups. In the intact tissues, GsMTx‐4 led to significant increases in CYM in hypertensive females, and normotensive males and females, but not in hypertensive males. In the denuded vessels, GsMTx‐4, produced a significant increase in CYM but only in the female normotensives. Differential expression of Piezo 1 were found in male versus female blood vessels. Our findings support a greater contribution of Piezo 1 mechanoceptors to vascular biomechanics of male hypertensive compared to male normotensive or female groups. The evidence also points to a possible differential vasoregulatory role for Piezo 1 in endothelial versus vascular smooth cells, with a greater contribution in males than females.
期刊介绍:
PR&P is jointly published by the American Society for Pharmacology and Experimental Therapeutics (ASPET), the British Pharmacological Society (BPS), and Wiley. PR&P is a bi-monthly open access journal that publishes a range of article types, including: target validation (preclinical papers that show a hypothesis is incorrect or papers on drugs that have failed in early clinical development); drug discovery reviews (strategy, hypotheses, and data resulting in a successful therapeutic drug); frontiers in translational medicine (drug and target validation for an unmet therapeutic need); pharmacological hypotheses (reviews that are oriented to inform a novel hypothesis); and replication studies (work that refutes key findings [failed replication] and work that validates key findings). PR&P publishes papers submitted directly to the journal and those referred from the journals of ASPET and the BPS