Endothelium-dependent vascular smooth muscle control

Recent pharmacologic evidence supports the importance of the integrity of the endothelium in modulating vascular reactivity. The endothelial cells produce one or more endothelium derived relaxing factor(s) or EDRF that cause relaxation of vascular smooth muscle cells through production of cyclic guanosine monophosphate (GMP) and subsequent activation of protein kinase. While the molecular pharmacology of vascular relaxation is now well defined and numerous factors have been identified that inhibit or stabilize EDRF, the chemical identity of EDRF still is uncertain. Nitric oxide appears to be one such EDRF. Alterations in vasoreactivity observed during surgical manipulation, trauma, inhalational anesthesia, atherosclerosis, and other disease states can now be explained by their influence on the endothelial cells and EDRF. Further, it is now clear that nitrovasodilators act directly on the vascular smooth muscle cell to produce biological intermediates that mimic the endogenous factors. While anesthesiologists and critical care physicians have traditionally focused on hormonal and nervous system control of vascular reactivity, the effects of various drugs and manipulations on EDRF appear to be of clinical importance. In this manuscript we review the pharmacology of EDRF and of exogenous nitrovasodilators with particular reference to factors that can modulate vasoreactivity.