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Departments of 1Pharmacobiology and 2Molecular Biomedicine, Centro de Investigación y de Estudios Avenzados de Instituto Politécnico Nacional, Mexico City; 3Pharmacology, Facultad Estudios Supeviores-Iztacala Universidad Nacional Autonoma de Mexico, México City; and 4Pathology, Instituto Nacional de Cardiología "Ignacio Chávez," Mexico City, Mexico
Submitted 10 June 2004 ; accepted in final form 30 August 2004
Angiotensin (ANG) II can be associated with gene expression regulation. Thus we studied the possible role of ANG II in the regulation of AT2 mRNA and protein expression. We utilized sham-operated renal ablation rats as well as renal ablation rats pretreated during the first 7 days of the development of renal damage with either the angiotensin-converting inhibitor ramipril, the AT1 receptor antagonist losartan, or the AT2 receptor antagonist PD-123319. Renal tissue was analyzed for histological changes and expression of AT2 receptor mRNA (by RT-PCR) and protein (by immunohistochemistry). To explore the physiological role of AT2 receptor overexpression in the development of renal damage, blood pressure, urinary protein excretion, and renal damage were evaluated. A time-dependent increase in the expression of AT2 receptor mRNA and protein was observed at 7, 15, and 30 days after renal ablation. Because these effects were already evident at day 7, the effects of ramipril, losartan, or PD-123319 were tested at this time. The ramipril group and the PD-123319-pretreated group showed inhibition of AT2 receptor expression, whereas the losartan-pretreated group showed a further increase in AT2 receptor expression. Inhibition of the AT2 receptor during renal ablation was associated with increased renal damage and a further increase in the blood pressure. This suggests that overexpression of AT2 receptors after renal ablation is modulated by ANG II through its own AT2 receptor and that functional expression of this effect may represent a counterregulatory mechanism to modulate the renal damage induced by renal ablation.
AT1 receptor; renovascular hypertension; losartan; PD-123319
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