CORONARY VENULAR RESPONSES TO FLOW AND PRESSURE

In previous studies, we demonstrated that both endothelium-dependent How-induced vasodilation and endothelium-independent myogenic responses occur in porcine coronary arterioles. However, it was not established whether these responses are present in the coronary venular microcirculation. The aim of this study was to test the hypotheses that 1) coronary venules, like arterioles, exhibit flow-induced dilation and myogenic responsiveness, and 2) venular How-induced dilation is endothelium-dependent and is mediated by the release of a nitrovasodilator. Experiments were performed in porcine subepicardial coronary venules, 80-120 mum in diameter, by using cannulated isolated vessel techniques to allow intraluminal pressure and flow to be independently controlled. Flow was initiated by simultaneously moving two perfusion reservoirs connected to the cannulating pipettes in equal amounts but in opposite directions. In the absence of How, i.e., zero pressure gradient (DELTAP) between the two reservoirs, venules developed spontaneous tone to 75-80% of maximum diameter at 10 cm H2O intraluminal pressure. Venules gradually dilated in response to stepwise increases in How (i.e.. DELTAP). The threshold for the flow-induced dilation occurred at DELTAP=1 cm H2O (flow=3.5 nl/sec), and the maximal response (dilation to 93+/-2% of maximum diameter) occurred when DELTAP was elevated to greater-than-or-equal-to 6 cm H2O flow=21 nl/sec at DELTAP=6 cm H2O). Flow-induced dilation was abolished after the endothelium was damaged by perfusion of an air bolus through the lumen. Vasoconstriction was observed when denuded venules were subjected to relatively high luminal flows (greater-than-or-equal-to 21 nl/sec). Flow-induced dilation was completely blocked after inhibition of nitrovasodilator synthesis by N(G)-monomethyl-L-arginine, and this inhibition was reversed by subsequent treatment with L-arginine. Coronary venules exhibited weak myogenic responses, and the venular pressure-diameter relation was not altered by endothelial denudation. From these results. we conclude that How-induced vasodilation in isolated porcine coronary venules is endothelium dependent and mediated by the release of a nitrovasodilator. Flow-induced constriction after endothelial removal suggests that vascular smooth muscle may respond directly to increases in shear stress.