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, Nomega-nitro-l-arginine methyl ester, or with Nomega-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.
Johnson
Fruzsina K
FK
Dept. of Physiology, Tulane University Health Sciences Center, 1430 Tulane Ave., SL39, New Orleans, LA 70112, USA. Fruzsi123@aol.com
Johnson
Robert A
RA
D000622:Aminolevulinic Acid / Q000378:metabolism; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002248:Carbon Monoxide / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*
D009569:Nitric Oxide; D002248:Carbon Monoxide; D000622:Aminolevulinic Acid; D006419:Heme Oxygenase (Decyclizing)