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Mechanosensitive G q/11 Protein–Coupled Receptors Mediate Myogenic Vasoconstriction
Author(s) -
Mederos y Schnitzler Michael,
Storch Ursula,
Gudermann Thomas
Publication year - 2016
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/micc.12293
Subject(s) - vasoconstriction , mechanosensitive channels , receptor , medicine , angiotensin ii , endocrinology , vascular smooth muscle , gq alpha subunit , chemistry , microbiology and biotechnology , biology , g protein coupled receptor , ion channel , smooth muscle
Myogenic vasoconstriction (Bayliss effect) is mediated by vascular smooth muscle cells (VSMCs) of small resistance arteries sensing mechanical forces. During the last three decades, several proteins have been proposed as VSMC mechanosensors. Our previous studies highlighted agonist‐independent mechanical activation of G q/11 protein‐coupled receptors (G q/11 PCR s) in VSMC s of resistance arteries. In particular, angiotensin II AT1 receptors ( AT 1 Rs) emerged as mechanosensors mediating myogenic tone. Moreover, we found that the AT 1B receptor isoform was more mechanosensitive than the AT 1A receptor. Interestingly, cysteinyl leukotriene 1 receptors (Cys LT 1 Rs) were up‐regulated in AT 1 R‐deficient arteries as an essential backup strategy to compensate for the loss of vasoconstrictor receptors. Up‐regulation of Cys LT 1 Rs resulted in increased myogenic tone at low intraluminal pressures resulting in hyperactivity of AT 1 R‐deficient arteries. Only at high intraluminal pressures myogenic tone was reduced, thus reflecting the loss of AT 1 Rs. Further, Cys LT 1 Rs were involved in myogenic vasoconstriction of wild‐type arteries. Simultaneous blockade of AT 1 Rs and Cys LT 1 Rs in wild‐type arteries caused reduction in myogenic tone of more than 60% comparable to the application of the selective G q/11 ‐protein inhibitor YM ‐254890. Our findings suggest that AT 1 Rs and Cys LT 1 Rs are crucial mechanosensors in resistance arteries mediating 60% of myogenic vasoconstriction via the G q/11 ‐protein pathway without involvement of endogenous agonists.