Hypertension Decreases Small Arteriole Responses to Acetylcholine in Skeletal Muscle

Abstract

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 × 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.

Key Words:

• hypertension
• microcirculation
• EDRF
• arterioles
• acetylcholine