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

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 69Ϯ3 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. (Hypertension. 2001;37:110-120.)

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

“…Both receptor subtypes for kinins can be expressed by the same cell types: vascular cells (endothelial, smooth muscle; Figueroa et al, 2001), nonvascular smooth muscle (e.g., uterine), fibroblasts (Ricupero et al, 2000), epithelial cells , nervous (afferent sensory) cells, and various tumor cells (Wu et al, 2002;Taub et al, 2003). There is an increasing interest in central nervous system localization of the kinin receptors and their regulation .…”

Review: Angiotensin-converting enzyme in skeletal muscle: sentinel of blood pressure control and glucose homeostasis

“…It should be stressed that all of the necessary components of the kinin system, including the precursor proteins, the enzyme that generates kinins, and the B 2 kinin receptors, are present in the endothelium of the nutritive vessels and in the red fibres of SMT. 26,54,[72][73][74][75] Vasodilation of these nutritive vessels in red muscle is completely endothelium-dependent, in contrast to the nutritive vessels of white muscle. 76 It is of interest to note that kinins display their vasodilating and metabolic actions not only in an endothelium-dependent manner, 63,64,[76][77][78] but also when applied interstitially.…”

“…[73][74][75]89 It is clear that further studies are needed to elucidate the molecular actions of kinins at their target cells. Furthermore, the functional significance of these new aspects in the kinin signalling cascade, reported recently by Erdös and coworkers, [192][193][194][195] are also functional in SMT and contribute to the overall improvement of muscle bioenergetics and glucose metabolism mediated by ACE-inhibitors.…”

“…This idea is supported by studies in myocardial tissue demonstrating that oxidative metabolism and myocardial performance is dependent on a balanced ACE activity. 75,198 Further investigations in this area are clearly required to more thoroughly evaluate this concept. …”

Bradykinin Contracts Rat Urinary Bladder Largely Independently of Phospholipase C

“…Among the known bradykinin receptor subtypes, the B1 receptor apparently is only poorly expressed in the healthy urinary bladder but becomes more prominent under pathophysiological conditions (Butt et al, 1995;Bellucci et al, 2007;Forner et al, 2012;Ribeiro et al, 2014). In contrast, B2 receptor expression has been shown at the mRNA (Chopra et al, 2005) and protein levels, as detected by radioligand binding (Figueroa et al, 2001) and immunohistochemistry (Chopra et al, 2005;Ribeiro et al, 2014). While recent findings question antibody-based data on receptor expression , the presence of B2 receptors in the bladder is also supported by considerable functional data.…”