Contribution of endogenous carbon monoxide to regulation of diameter in resistance vessels.
Endogenous carbon monoxide was proposed to subserve vasodepressor functions. If so, inhibition of heme oxygenase may be expected to promote vascular contraction. This hypothesis was examined in large and small arteries and in isolated first-order gracilis muscle arterioles of rat. The heme oxygenase inhibitors chromium mesoporphyrin (CrMP) and cobalt protoporphyrin (0.175-102 micromol/l) decreased the diameter of pressurized (80 mmHg) gracilis muscle arterioles, whereas magnesium protoporphyrin, a weak heme oxygenase inhibitor, did not. CrMP also elicited development of isometric tension in the muscular branch of the femoral artery but not in the aorta or femoral artery. Arteriolar constrictor responses to CrMP varied in relation to the intravascular pressure, were blunted in preparations exposed to exogenous carbon monoxide (100 micromol/l), and were unaffected by an endothelin receptor antagonist. Importantly, CrMP amplified the constrictor response to increases of pressure in gracilis arterioles. Accordingly, the constrictor effect of heme oxygenase inhibitors is attributable to magnification of myogenic tone due to withdrawal of a vasodilatory mechanism mediated by endogenous carbon monoxide. The study suggests that the vascular carbon monoxide system plays a role in the regulation of basal tone in resistance vessels.
Kozma
F
F
Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA.
Johnson
R A
RA
Zhang
F
F
Yu
C
C
Tong
X
X
Nasjletti
A
A
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology*; D002857:Chromium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors; D006614:Hindlimb; D066298:In Vitro Techniques; D008297:Male; D008652:Mesoporphyrins / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D014655:Vascular Resistance / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
D004791:Enzyme Inhibitors; D008652:Mesoporphyrins; D008665:Metalloporphyrins; D002857:Chromium; C031468:mesoporphyrin IX; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)