Differential Distribution of Bradykinin B 2 Receptors in the Rat and Human Cardiovascular System

Author:

Figueroa Carlos D.1,Marchant Alejandra1,Novoa Ulises1,Förstermann Ulrich1,Jarnagin Kurt1,Schölkens Bernward1,Müller-Esterl Werner1

Affiliation:

1. From the Instituto de Histologia y Patologia (C.D.F., A.M., U.N.), Universidad Austral de Chile, Valdivia, Chile; Department of Pharmacology (U.F.), Johannes Gutenberg University, Mainz, Germany; Iconix Pharmaceuticals (K.J.), Mountain View, Calif; Aventis (B.S.), Frankfurt, Germany; and Institute for Biochemistry II (W.M.-E.), Johann Wolfgang Goethe University, Frankfurt, Germany.

Abstract

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 B 2 receptor in the cardiovascular system is not precisely known. Immunoblot analysis with an anti-peptide antibody to the bradykinin B 2 receptor or chemical cross-linkage with [ 125 I]Tyr 0 -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 B 2 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 B 2 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 B 2 receptor in arterioles is not a species-specific phenomenon. During development, the distribution of B 2 receptor in the heart changes; for example, in the heart of newborn rats, the B 2 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, B 2 receptors are localized differentially in different parts of the cardiovascular system: the arterioles have smooth muscle–localized B 2 receptors, and large elastic vessels have endothelium-localized receptors.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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