MAPPING OF ANGIOTENSIN II RECEPTOR SUBTYPES IN PERIPHERAL TISSUES OF SPONTANEOUSLY HYPERTENSIVE RATS BY IN VITRO AUTORADIOGRAPHY

Abstract

1. The regulation of angiotensin I1 (AII) receptor subtypes was studied in peripheral tissues of 20 week old male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) rats.2. A11 receptor binding was determined by a quantitative in vitro autoradiography using [125I]-[Sar1,Iles]AII as a ligand on the kidney, adrenal gland, thoracic aorta and heart. CV-11974, a specific AT1 receptor antagonist, and CGP42112B, a specific AT2 antagonist, were used in competition with [125I]-[Sarl,Iles]AII to differentiate AT1 and AT2 receptor binding.3. The relative abundance of each subtype was very similar between SHR and WKY rats. In both strains of rats, the adrenal cortex contained predominantly AT1 receptors, while AT2 receptors predominated in the adrenal medulla. The kidney contained exclusively AT1 receptors over glomeruli, proximal tubules and outer medulla. AT1 receptors were predominant in the thoracic aorta and heart. 4.As for relative receptor density, important differences were observed between SHR and WKY rats. In SHR, the adrenal cortex, outer medulla of the kidney, and heart displayed higher AT1 receptor density than WKY rats. 5.These results indicate that the expression of AT1 receptors is differently regulated in some important targets of A11 in SHR, and suggest that the altered regulation of AT1 receptor presented in this study should be relevant to the pathophysiological features of SHR.

Angiotensin II type 2 receptor overexpression activates the vascular kinin system and causes vasodilation

“…The data indicated localization of AT2 throughout the aortic wall (including the medial layer), although the cellular localization of AT2 was not defined. Similar results were obtained in Wistar-Kyoto and spontaneously hypertensive rats (7). Endothelial cells derived from coronary arteries of spontaneously hypertensive rats express AT1 and AT2 in an 80:20 ratio (46).…”

“…Because AT2 is present in microvessels at high levels (6)(7)(8), and AT2 activation is increased in atherosclerosis lesions of the aorta (55) and neointima after vascular injury (56), the AT2-mediated depressor effect of the bradykinin/NO system is expected to contribute to the management of BP, coronary microcirculation, and vascular remodeling with AT1 antagonists. We believe we have shown that AT2 stimulation has a novel hemodynamic effect by inhibiting AT1-mediated chronotropic actions without affecting cardiac contractility (24).…”

“…Treatment with AT1 antagonists causes elevation of plasma Ang II, which selectively binds to AT2 and exerts clinically important, but as yet undefined, effects (5). Although the level of AT2 expression is low in large vessels such as the aorta, AT2 is present at high levels in microvessels (6)(7)(8). Ichiki et al (9) and Hein et al (10) reported that disruption of the AT2 gene caused an increase in blood pressure (BP) and increased sensitivity to the pressor action of Ang II.…”

AT2 Receptors Attenuate AT1 Receptor-Induced Phospholipase D Activation in Vascular Smooth Muscle Cells

“…It should be noted that previous reports did not identify AT 2 receptors in the renal vasculature (Song et al, 1994;Song et al, 1995;Haddad and Garcia, 1996;Gao et al, 2003). Indeed, we have been unable to detect AT 2 receptors in freshly isolated preglomerular microvessels from either WKY or SHR using either Western blots or RT-PCR (Gao et al, 2003).…”

Interaction of Angiotensin II Type 1 and D 5 Dopamine Receptors in Renal Proximal Tubule Cells

“…However, it is realized that the renal expression of AT 1 receptors in SHR has not been consistently shown to be elevated. [45][46][47][48][49][50][51][52] For example, ovariectomy or salt loading in SHR increases renal AT 1 receptors. 44,45 However, renal outer medullary but not cortical AT 1 expression has been reported to be increased in SHR relative to WKY.…”