Application of Drug–Receptor Theories to Angiotensin

Abstract
The myotropic action of angiotensin II has been studied on two smooth muscle preparations: the strip of rat stomach and of rabbit thoracic aorta. Contractions evoked by angiotensin are not modified by atropine, methysergide, and diphenhydramine on the rat stomach or by phentolamine, methysergide, and diphenhydramine on the rabbit aorta. It appears that angiotensin acts directly on specific receptors and not through release of acetylcholine on the stomach or of noradrenaline on the aorta. Interference by intramural prostaglandins is excluded because angiotensin is equally active on tissues pretreated or not with indomethacin.Dose–response curves obtained with angiotensin on the two tissues are close to the theoretical curves predicted by the mass–action law. The relations stimulus effect is linear, indicating that the extent of the contraction is proportional to the number of receptors occupied by the agonist. No threshold phenomenon or spare receptor capacity could be demonstrated in either tissue. It is therefore concluded that the interaction of angiotensin with its specific receptors in the two smooth muscle preparations can be analyzed quantitatively with the occupation theory by applying the concepts of affinity and intrinsic activity as defined by Ariens in 1964. (Molecular pharmacology. Vol. 1. The mode of action of biologically active compounds. Academic Press, New York.)