1.Negative regulation of RhoA/Rho kinase by angiotensin II type 2 receptor in vascular smooth muscle cells: role in angiotensin II-induced vasodilation in stroke-prone spontaneously hypertensive rats.
Savoia C;Tabet F;Yao G;Schiffrin EL;Touyz RM J Hypertens. 2005 May;23(5):1037-45.
OBJECTIVE: ;To test whether angiotensin II (Ang II) through the Ang II type 2 receptor (AT2R), downregulates RhoA/Rho kinase, which plays a role in AT1 receptor (AT1R)-mediated function.;METHODS: ;In vitro studies were performed in A10 vascular smooth muscle cells (VSMC) and in vivo studies in mesenteric arteries from Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats. VSMC were stimulated with Ang II (10 mol/l), CGP42112A (10 mol/l, a selective AT2R agonist) +/- valsartan (10 mol/l, an AT1R antagonist), or the Rho kinase inhibitor fasudil (10 mol/l). AT1R and AT2R expression and myosin light chain (MLC) phosphorylation were determined by immunoblotting. RhoA activity was assessed by measuring membrane translocation. Functional significance between AT2R, RhoA/Rho kinase and vasodilation was assessed in arteries from valsartan-treated (30 mg/kg per day, 14 days) WKY and SHRSP rats. Vasodilatory responses to Ang II (10-10 mol/l) were performed in norepinephrine pre-contracted vessels +/- valsartan(10 mol/l), PD123319 (10 mol/l, an AT2R antagonist) or fasudil (10 mol/l).;RESULTS: ;A10 VSMC expressed AT1R and AT2R. In valsartan-treated cells, Ang II-induced RhoA translocation was reduced versus controls (42 +/- 6%, P < 0.
2.[Angiotensin II receptor subtype in human adrenal glands].
Tanabe A;Naruse M;Naruse K;Yoshimoto T;Tanaka M;Mishina N;Imaki T;Sugaya K;Miyazaki H;Demura H Nihon Rinsho. 1999 May;57(5):1042-8.
Although adrenal gland is one of the major target organs of angiotensin II (Ang II), the pathophysiological significance of the its receptor subtype has not been elucidated. We demonstrated by reverse transcription-polymerase chain reaction with Southern blot analysis mRNA expression of both AT1 and AT2 in human adrenal tissues of normal adrenocortical tissues, aldosterone-producing adenoma, Cushing's syndrome, and pheochromocytoma. Ang II-induced aldosterone secretion in vitro was suppressed only by 50% in the presence of selective AT1 antagonist CV-11974, while AT2 agonist CGP-42112 increased aldosterone secretion by 55% over the control. Ang II or CGP-42112 did not affect cortisol secretion. In addition, Ang II could stimulate aldosterone secretion in AT1a knockout mice both in the presence and absence of CV-11974. These results suggest that non-AT1 receptor subtype(s) including AT2, as well as AT1, is involved in the stimulation of aldosterone secretion from human adrenals.
3.Expression of a novel non-angiotensin II [125I]CGP 42112 binding site in healing wounds of the rat brain.
Viswanathan M;de Oliveira AM;Correa FM;Saavedra JM Brain Res. 1994 Sep 26;658(1-2):265-70.
We characterized a novel non-angiotensin II binding site that is recognized by the angiotensin II AT2 receptor ligand [125I]CGP 42112, in healing brain wounds of adult rats. The binding, which was highest at 3 days after injury, appears to be localized to activated microglia surrounding the wound. The novel CGP 42112 binding site may have a role in the function of microglia and in mechanisms of tissue repair in the brain.
