Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles

Vascular tissues express heme oxygenase, which metabolizes heme to form carbon monoxide ( CO). CO promotes relaxation of vascular smooth muscle but also inhibits nitric oxide ( NO) formation. This study examines the hypothesis that CO promotes endothelium- and NO synthase-dependent vasoconstriction of isolated arterioles. Studies were conducted on pressurized first-order gracilis muscle arterioles isolated from anesthetized male Sprague-Dawley rats. Exogenous CO, as well as a heme precursor, delta-aminolevulinic acid (delta-ALA), constricted arterioles with intact endothelium pretreated with phenylephrine; these effects were abolished by removal of the endothelium. CO- and delta-ALA-induced vasoconstrictions were converted to dilations by pretreatment with an inhibitor of NO synthase, N-omega-nitro-L-arginine methyl ester, or with N-omega-nitro-L-arginine methyl ester and an NO donor, sodium nitroprusside. Furthermore, CO- induced vasoconstriction was prevented by pretreatment with the NO synthase substrate L-arginine. This study shows that exogenous, as well as endogenously formed, CO can promote endothelium-dependent vasoconstriction in isolated gracilis muscle arterioles. Because CO- induced vasoconstriction is abolished by NO synthase blockade and by L-arginine, CO most likely promotes endothelium- dependent vasoconstriction by inhibiting endothelial NO formation.