The distal steps of the signalling cascade leading to myogenic constriction in vascular smooth muscle cells (SMCs) have been well investigated, while sensing and the proximal steps are enigmatic. The three cation channels TRPC3, 6 and 7 represent likely molecular candidates for channels involved in receptor-operated cation entry causing depolarization followed by the activation of voltage-gated L-type Ca²⁺ channels in SMCs. These channels are activated after Gq-coupled receptor-mediated stimulation of PLC. Here we show that mechanical membrane stretch and osmotic cell swelling activate Gq-coupled receptors without involvement of agonists. Using BRET, b-arrestin was shown to be recruited to the receptor in a way similar to agonist stimulation. Receptor activation and the subsequent signalling cascade that results in channel activation can be blocked at different levels. We show that Gq-coupled receptors like AT₁ angiotensin II and ET_A receptors can be activated by mechanical or osmotic stress. Elevated expression levels of AT₁ receptors in A7r5 cells lead to sensitivity to membrane stretch and TRPC6 activation. In isolated cerebral arteries, myogenic tone is profoundly diminished after incubation with the AT₁ receptor antagonist losartan. Thus, Gq-coupled receptors are important components of mechanosensory complex in vascular SMCs.