The role of endothelium in the control of vascular tone.

In the last few years, experimental evidence has accumulated which suggests a substantial role for the endothelium in the control of vascular tone. Endothelium-dependent dilatations have been demonstrated in various arteries of numerous mammalian species including man. Among the stimuli which elicit endothelium-dependent dilatation are such varying stimuli as increases in blood flow and hypoxia, as well as endogenous (acetylcholine, ATP, ADP, bradykinin, substance P) and pharmacological agents (calcium ionophore A 23187, ergometrine, hydralazine, melittin). The functional importance of endothelium-dependent dilatation is emphasized by the fact that the direct vasoconstrictor effects of some of these substances (acetylcholine, histamine, norepinephrine, serotonin) on vascular smooth muscle is attenuated or even reversed by their simultaneous stimulatory effect on endothelial cells, resulting in the release of a vasodilator signal. Bioassay experiments have shown that a humoral vasodilator agent with a biological half-life in the range of seconds is released from the endothelium (native or cultured) during stimulation with acetylcholine, ATP and calcium ionophore. Experimental data are presented, which suggest that EDRF may act by direct stimulation of guanylate cyclase, resulting in smooth muscle relaxation due to increased smooth muscle cyclic GMP levels. The chemical nature of this nonprostaglandin endothelium-derived relaxant factor (EDRF) is still not known. The possible physiological and pathophysiological significance of endothelium-dependent dilatation in situ is discussed. Special attention is paid in this context to the potential role of EDRF activity in coronary vasomotor control.