Mechanosensitive G Protein-Coupled Receptors Mediate Myogenic Vasoconstriction.

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