Characteristics of heterogeneity in the expression of vasoconstriction in response to NG-monomethyl-L-arginine in isolated canine arteries

We characterized the contractile effect of a nitric oxide (NO) synthase inhibitor, N-G-monomethyl-L-arginine (L-NMMA), in isolated canine arteries. L-NMMA induced a heterogenous response: potent vasoconstriction in the cerebral arteries, and weak or no vasoconstrictor responses in different peripheral arteries. The vasoconstriction of the cerebral artery was inhibited by L-arginine but not D-arginine. L-NMMA(10(-4) M) caused a 53% decrease in guanosine 3'5'-cyclic monophosphate (cGMP) levels in the cerebral artery, but it was not significant compared with that in peripheral arteries. The L-NMMA-induced vasoconstriction was inhibited by diltiazem and nicardipine, and the heterogeneity was mimicked by treatment with charybdotoxin, a Ca2+-activated K+ (BKCa) channel blocker, channels which are regulated by NO/cGMP. Both L-NMMA and charybdotoxin caused a potent vasoconstriction in the mesenteric artery precontracted with 20 mM KCl. 1 H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ) (10(-5) M), a selective guanylate cyclase inhibitor, caused vasoconstriction in the presence of nitroprusside in the endothelium-denuded basilar artery, but not in the endothelium-denuded mesenteric artery. In conclusion, LNMMA-induced heterogenous vasoconstriction was due to the different sensitivities of vascular smooth muscles to NO/cGMP. The heterogeneity may result from a difference in the basal state of ion channels such as the voltage-dependent Ca2+ channel and the BKCa channel in vascular smooth muscles. (C) 1999 Elsevier Science B.V. All rights reserved.