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This Article Full Text Full Text (PDF) All Versions of this Article: 288/1/F207    most recent 00216.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Vázquez, E. Articles by Escalante, B. Search for Related Content PubMed PubMed Citation Articles by Vázquez, E. Articles by Escalante, B.

Angiotensin II-dependent induction of AT₂ receptor expression after renal ablation

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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