The purpose of the present study was to test the hypothesis that adenylate cyclase activity of porcine coronary artery smooth muscle cells is sensitive to mechanical stretch. Cultured vascular smooth muscle cells were stretched at 24% maximal strain at 60 cycles/min for 30 minutes. Both basal and maximal catalytic activity of adenylate cyclase (as assessed by stimulation by 100 microM forskolin with 5 mM manganese chloride) were reduced by 30% (P less than 0.05) in membranes obtained from stretch versus unstretched cells. The magnitude of the stretch-induced reduction in Gpp(NH)p was identical over the entire time course studied (5-30 minutes). Furthermore, basal adenylate cyclase activity was inversely related to the magnitude of stretch. Thus, cyclic stretch can influence adenylate cyclase activity in coronary vascular smooth muscle cells. These data provide important information concerning potential biochemical mechanisms involved in the myogenic response of vascular smooth muscle and also suggest a potential mechanism by which the coronary circulation may adapt to chronically reduced perfusion pressure.