Endothelium-Dependent Relaxation in Systemic Arteries

The ability of acetylcholine and other muscarinic agonists to produce marked vasodilatation in various vascular beds in vivo was well established many years ago. In view of the potent vasodilating activity of muscarinic agonists in vivo, it was to be expected that these agents would produce relaxation of isolated blood vessels in vitro. More than 13 years ago it was demonstrated in a number of laboratories that acetylcholine and other muscarinic agonists could indeed produce relaxation (dilatation) of isolated perfused or superfused blood vessels contracted by stimulation of perivascular adrenergic nerves (e.g., Rand and Varma, 1970; Hume et al., 1972; Steinsland et al., 1973; Vanhoutte, 1974, 1977). This relaxation was attributed to an action of muscarinic agonists on the muscarinic “inhibitory receptor” of adrenergic nerve endings (Loffelholz and Muscholl, 1969), resulting in inhibition of release of norepinephrine from these terminals. This prejunctional inhibitory action of muscarinic agonists could explain in part the vasodilatation that they produced in innervated vascular beds in vivo; but it could not explain the ability of these agents to still cause marked dilatation in denervated vascular beds. In view of such vasodilatation, it was to be expected that muscarinic agonists would produce relaxation of spontaneous or drug-induced contractions of isolated preparations of blood vessels.