The myogenic response, an active constriction and dilation of vessels to changes in intravascular pressure, can play an important role in the regulation of coronary blood flow. The characteristics of the myogenic response and its modulation by endothelium-derived factors are organ and location specific and have not been studied extensively in intramural coronary arterioles. Thus, distal intramural branches (approximately 100 and approximately 170 microm active and passive diameter, respectively) of the left anterior descending coronary artery of rats were isolated and cannulated. Step increases in intraluminal pressure from 0 to 40 mm Hg elicited increases in diameter, whereas further increases in pressure from 50 to 150 mm Hg resulted in constrictions. In control, the pressure-induced myogenic tone of coronary arterioles was 67.3 +/- 2.7% of passive diameter (PD, obtained in Ca2+-free solution) at 60 mm Hg. Nomega-nitro-L-arginine (L-NNA, 10(-5) M), an inhibitor of nitric oxide synthase, reduced the initial arteriolar diameter (by 44.8 +/- 5.1 microm at 2 mm Hg, P < 0.05) and significantly mitigated increases in diameter to lower pressures and constrictions to higher pressures (41.1 +/- 5.6% of PD at 60 mm Hg). Administration of adenosine restored the initial diameter in the presence of l-NNA, but the increase in diameter to lower pressures and the decrease in diameter to higher pressures observed under control conditions remained greatly inhibited. Inhibition of prostaglandin synthesis, or PGH2/TxA2 receptors significantly reduced the constrictions to higher pressures as compared with control (indomethacin: from 57.9 +/- 4.8% of PD to 67.0 +/- 4.7% of PD at 150 mm Hg). Thus, because in isolated intramural coronary arterioles of rats a negative slope for the pressure-diameter curve develops only in the presence of nitric oxide and constrictor prostaglandins, they seem to be essential for the normal development of the myogenic response.