INTERACTION OF PRESSURE-INDUCED AND FLOW-INDUCED RESPONSES IN PORCINE CORONARY RESISTANCE VESSELS

Pressure-induced myogenic responses and flow-induced vasodilatory responses have been documented in coronary resistance arterioles, but the interaction of these two mechanisms and the nature of the flow-mediated response are not well understood. Experiments were designed to quantitatively study the interaction of pressure- and flow-induced responses and to characterize the nature of the substance responsible for flow-mediated dilation in isolated coronary arterioles. Subepicardial arterioles (40-80-mu-m) were isolated from pigs and cannulated with two glass micropipettes and then pressurized via independent reservoir systems. Flow was initiated by simultaneously moving the reservoirs in equal and opposite directions thus generating a pressure gradient (DELTA-P) without changing the mean intraluminal pressure (IP). IP was changed by moving both reservoirs in the same direction to alter myogenic tone in the absence of flow (DELTA-P = 0). Flow-mediated dilation competed with myogenic constriction when flow and pressure were elevated. Also, flow potentiated myogenic dilation when IP was decreased. The magnitude of flow-induced dilation was greatest at an intermediate level of vascular tone (IP = 60 cmH2O) but was attenuated at higher and lower levels of tone. In the presence of flow (DELTA-P = 4 cmH2O), pressure-diameter relationships were shifted upward, and the magnitude of myogenic responsiveness was attenuated. Double-vessel bioassay studies indicated that a transferable substance was released from intact endothelium in response to flow. Flow-induced dilation was not affected by indomethacin but was abolished by N(G)-monomethyl-L-arginine or by mechanical removal of endothelium. Our results indicate that pressure- and flow-induced responses closely interact either competitively or additively, depending on the direction of local vascular pressure changes. Moreover, flow-induced dilation was mediated by the release of a transferable nitrovasodilator rather than a prostanoid from endothelial cells.