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 less than 0.05) inhibited endothelium-dependent relaxations to the receptor-mediated methacholine and the nonreceptor-mediated A23187. Bupivacaine was more potent (P less than 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.
Johns
R A
RA
Department of Anesthesiology, University of Virginia Health Sciences Center, Charlottesville 22908.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002045:Bupivacaine / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D005041:Etidocaine / Q000494:pharmacology; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D011343:Procaine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects*
D000779:Anesthetics, Local; D011343:Procaine; C004616:chloroprocaine; D008012:Lidocaine; D005041:Etidocaine; D002045:Bupivacaine