Control of microvascular resistance in physiological conditions and reperfusion

Regulation of coronary microvascular resistance is not distributed uniformly, but varies across different segments of the vasculature. Differences in regulatory mechanisms, including metabolic, myogenic, alpha-adrenergic and endothelial cell mediated, help define a series of coronary vascular microdomains. Generally, small arterioles, those less than 100 microns in diameter, respond differently than large arterioles or small arteries. This segmental distribution suggests an integrative hypothesis of regulation whereby a variety of mechanisms play a role in the overall response. One pathology that disturbs these control mechanisms in the microcirculation of the heart is reperfusion injury. Reperfusion injury of the microcirculation has as its primary target the vascular endothelium. The mechanisms responsible for reduced endothelium-dependent relaxation, likely include a reduction in the levels of tetrahydrobiopterin, a co-factor of nitric oxide synthase. Manipulation of levels of tetrahydrobiopterin in endothelial cells may be beneficial in the prevention of the pathophysiological sequelae of reperfusion injury in the coronary microcirculation.