Differential distribution of bradykinin B2 receptors in the rat and human cardiovascular system

Abstract

Bradykinin, a major vasodilator peptide, plays an important role in the local regulation of blood pressure, blood flow, and vascular permeability; however, the cellular distribution of the major bradykinin B2 receptor in the cardiovascular system is not precisely known. Immunoblot analysis with an anti-peptide antibody to the bradykinin B2 receptor or chemical cross-linkage with [125I]Tyr0-bradykinin revealed a band of 69±3 kDa at varying intensity in the homogenates of the endothelium and tunica media of the rat aorta and endocardium. Immunostaining showed that the B2 receptor is abundant in the endothelial linings of the aorta, other elastic arteries, muscular arteries, capillaries, venules, and large veins, where it localizes preferentially to the luminal face of the endothelial cells. In marked contrast, small arterioles (ie, the principal blood-pressure regulating vessels) of the mesenterium, heart, urinary bladder, brain, salivary gland, and kidney had a different staining pattern in which B2 receptor was prominent in the perivascular smooth muscle cells of the tunica media. A similar distribution pattern was found in mouse as well as in human tissues, indicating that the particular distribution pattern of the B2 receptor in arterioles is not a species-specific phenomenon. During development, the distribution of B2 receptor in the heart changes; for example, in the heart of newborn rats, the B2 receptor was abundant in the myocardium, whereas in the adult heart, the receptor was present in the endocardium of atria, atrioventricular valves, and ventricles but not in the myocardium. Thus, B2 receptors are localized differentially in different parts of the cardiovascular system: the arterioles have smooth muscle-localized B2 receptors, and large elastic vessels have endothelium-localized receptors.