Vasoregulatory function of the heme-heme oxygenase-carbon monoxide system.
Arterial vessels express one or more heme oxygenase (HO) isoenzymes that catalyze the metabolism of heme to carbon monoxide (CO) and biliverdin. Carbon monoxide promotes vasorelaxation through mechanisms that, depending on the vessels, involve activation of soluble guanylate cyclase, stimulation of calcium-activated potassium channels, or diminished synthesis of constrictor mediators, such as, endothelin and 20-HETE. Inhibitors of HO elicit vasoconstriction in vivo and in isolated pressurized arterioles. Inhibitors of HO also enhance myogenic vasoconstriction, as well as the constriction induced by phenylephrine in several vessels. The blood pressure of awake rats is increased by acute treatment with HO inhibitors, a response that is accompanied by attenuation of baroreflex activity. All in all, it would appear that a product of HO activity manufactured by arterial vessels, presumably CO, promotes vasodilation and decreases the reactivity of vascular smooth muscle to myogenic stimuli and constrictor agonists. In doing so, CO of vascular origin may contribute to the implementation of antihypertensive mechanisms. Carbon monoxide produced in central nervous system structures, for example, the nucleus tractus solitarii, also appears to support a blood pressure-lowering mechanism linked to inhibitory modulation of baroreceptor reflex activity.
Zhang
F
F
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Kaide
J I
JI
Rodriguez-Mulero
F
F
Abraham
N G
NG
Nasjletti
A
A
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D002248:Carbon Monoxide / Q000494:pharmacology / Q000502:physiology*; D006418:Heme / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*
D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)