HYPERTENSION DECREASES SMALL ARTERIOLE RESPONSES TO ACETYLCHOLINE IN SKELETAL-MUSCLE

Television microscopy was used to quantitate in vivo the responses of skeletal muscle small arterioles to acetylcholine. Five groups of rats were used: normotensive and one (1K1C)- and two (2K1C)- kidney one clip renovascular hypertensive Sprague-Dawley rats (SDR), as well as WKY normotensive and spontaneously hypertensive (SHR) rats. Third-order arterioles dilated to acetylcholine with an EC50 of 3 x 10(-7) M in SDR and 10(-6) M in WKY animals. In contrast, the concentration-response curve to acetylcholine was shifted to the right (less reactive) by 100 fold in the 1K1C- and by 1000 fold in the 2K1C-hypertensives. The dose-responsive curve to acetylcholine was shifted 10-fold to the right in the SHR's compared to the WKY's. Because acetylcholine acts through endothelium-dependent mechanisms and because maximal vasodilation could be induced by an endothelium-independent vasodilator, Na-nitroprusside, in all but the 2K1C-group, we conclude that different forms of hypertension interfere to a variable degree with endothelium-dependent vasodilator mechanisms in the skeletal muscle microcirculation.