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 c ontraction. 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 mu mol/l) decreased the diameter of pressurized (80 mmHg) gracilis musc le arterioles, whereas magnesium protoporphyrin, a weak heme oxygenase inhi bitor, did not. CrMP also elicited development of isometric tension in the muscular branch of the femoral artery but not in the aorta or femoral arter y. Arteriolar constrictor responses to CrMP varied in relation to the intra vascular pressure, were blunted in preparations exposed to exogenous carbon monoxide (100 mu mol/l), and were unaffected by an endothelin receptor ant agonist. 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 carbo n monoxide. The study suggests that the vascular carbon monoxide system pla ys a role in the regulation of basal tone in resistance vessels.