The heme oxygenase-carbon monoxide system as a regulator of microvascular function

Heme oxygenase (HO) catalyzes oxidative cleavage of protoheme IX to generate divalent iron, biliverdin, and carbon monoxide (CO). The interest in the HO-CO system has emerged in numerous disciplines among such as cardiovascular physiology, the central nervous and hepatic microvascular systems. Although for many years products of the HO reaction had been regarded as potentially toxic wastes, recent studies have implicated that these products play physiological roles. Both NO and CO share the ability to bind to the prosthetic group of heme proteins, structural changes and the functional outcomes of the proteins seem quite different between the oases. Differences in effects on soluble guanylate cyclase and hemoglobin between NO and CO led us to understand mechanisms as to how the proteins can distinguish the gases to transducer signals in distinct ways. This chapter focuses on recent advances in both physiologic and pathophysiologic roles of CO and aims to provide updated information on these gas mediators as potential regulators of the organ function on the basis of data collected from the model of isolated perfused liver of rats.