Local anesthetics inhibit endothelium-dependent vasodilation

The effect of local anesthetics on endothelium-dependent and endothelium-independent vasodilation was determined using isolated rat thoracic aorta. Endothelium-intact rat aortic rings were mounted for isometric tension recording. Cumulative concentration-dependent vascular relaxation responses to the endothelium-dependent vasodilators methacholine (1 x 10^-8 to 3 x 10^-5 M), the calcium ionophore A23187 (1 x 10^-8 to 3 x 10^-7 M) and the endothelium-independent vasodilator sodium nitroprusside (1 x 10^-9 to 1 x 10^-7 M) were determined in the presence or absence of bupivacaine, lidocaine, etidocaine, or 2-chloroprocaine (1 x 10^-4 M). All of the local anesthetics studied significantly (P < 0.05) inhibited endothelium-dependent relaxations to the receptor-mediated methacholine and the nonreceptor-mediated A23187. Bupivacaine was more potent (P < 0.01) than the other three anesthetics tested. Direct, endothelium-independent vasodilation by sodium nitroprusside was not affected. The local anesthetics appear to exert their inhibitory effect on endothelium-dependent vasodilation at a site distal to receptor activation at the endothelial cell and proximal to guanylate cyclase activation in the vascular smooth muscle.