Carbon monoxide: from toxin to endogenous modulator of cardiovascular functions

Carbon monoxide (CO) is a pollutant commonly recognized for its toxicologic al attributes, including CNS and cardiovascular effects. But CO is also for med endogenously in mammalian tissues. Endogenously formed CO normally aris es from heme degradation in a reaction catalyzed by heme oxygenase. While i nhibitors of endogenous CO production can raise arterial pressure, heme loa ding can enhance CO production and lead to vasodepression. Both central and peripheral tissues possess heme oxygenases and generate CO from heme, but the inability of heme substrate to cross the blood brain barrier suggests t he CNS heme-heme oxygenase-CO system may be independent of the periphery. I n the CNS, CO apparently acts in the nucleus tractus solitarii (NTS) promot ing changes in glutamatergic neurotransmission and lowering blood pressure. At the periphery, the heme-heme oxygenase-CO system can affect cardiovascu lar functions in a two-fold manner; specifically: 1) heme-derived CO genera ted within vascular smooth muscle (VSM) can promote vasodilation, but 2) it s actions on the endothelium apparently can promote vasoconstriction. Thus, it seems reasonable that the CNS-, VSM- and endothelial-dependent actions of the heme-heme oxygenase-CO system may all affect cardiac output and vasc ular resistance, and subsequently blood pressure.