Mechanosensitive Gq/11 Protein–Coupled Receptors Mediate Myogenic Vasoconstriction

AbstractMyogenic 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 Gq/11 protein‐coupled receptors (Gq/11PCRs) in VSMCs of resistance arteries. In particular, angiotensin II AT1 receptors (AT1Rs) emerged as mechanosensors mediating myogenic tone. Moreover, we found that the AT1B receptor isoform was more mechanosensitive than the AT1A receptor. Interestingly, cysteinyl leukotriene 1 receptors (CysLT1Rs) were up‐regulated in AT1R‐deficient arteries as an essential backup strategy to compensate for the loss of vasoconstrictor receptors. Up‐regulation of CysLT1Rs resulted in increased myogenic tone at low intraluminal pressures resulting in hyperactivity of AT1R‐deficient arteries. Only at high intraluminal pressures myogenic tone was reduced, thus reflecting the loss of AT1Rs. Further, CysLT1Rs were involved in myogenic vasoconstriction of wild‐type arteries. Simultaneous blockade of AT1Rs and CysLT1Rs in wild‐type arteries caused reduction in myogenic tone of more than 60% comparable to the application of the selective Gq/11‐protein inhibitor YM‐254890. Our findings suggest that AT1Rs and CysLT1Rs are crucial mechanosensors in resistance arteries mediating 60% of myogenic vasoconstriction via the Gq/11‐protein pathway without involvement of endogenous agonists.