Novel role of mechanosensitive AT1B receptors in myogenic vasoconstriction - PubMed (original) (raw)
. 2014 Jul;466(7):1343-53.
doi: 10.1007/s00424-013-1372-3. Epub 2013 Oct 8.
Affiliations
- PMID: 24101294
- DOI: 10.1007/s00424-013-1372-3
Novel role of mechanosensitive AT1B receptors in myogenic vasoconstriction
Stephanie Blodow et al. Pflugers Arch. 2014 Jul.
Abstract
Myogenic vasoconstriction is an inherent property of vascular smooth muscle cells (VSMCs) of resistance arteries harboring ill-defined mechanosensing and mechanotransducing elements. G protein-coupled receptors (GPCRs) are discussed as mechanosensors in VSMCs. In this study, we sought to identify and characterize the role and impact of GPCRs on myogenic vasoconstriction. Thus, we analyzed mRNA expression levels of GPCRs in resistance versus preceding conduit arteries revealing a significant enrichment of several GPCRs in resistance vessels. Selective pharmacological blockade of the highly expressed GPCRs in isolated murine mesenteric arteries ex vivo decreased myogenic vasoconstriction. In particular, candesartan and losartan most prominently suppressed myogenic tone, suggesting that AT1 receptors play a central role in myogenic vasoconstriction. Analyzing angiotensinogen(-/-) mice, a relevant contribution of locally produced angiotensin II to myogenic tone could be excluded. Investigation of AT1A (-/-) and AT1B (-/-) murine mesenteric arteries revealed that AT1B, but not AT1A, receptors are key components of myogenic regulation. This notion was supported by examining fura-2-loaded isolated AT1A (-/-) and AT1B (-/-) VSMCs. Our results indicate that in VSMCs, AT1B receptors are more mechanosensitive than AT1A receptors even at comparable receptor expression levels. Furthermore, we demonstrate that the mechanosensitivity of GPCRs is agonist-independent and positively correlates with receptor expression levels.
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