Am J Physiol Renal Physiol
Department of Pharmacobiology, CINVESTAV-IPN, Av. Instituto Politécnico Nacional 2508, CP 07360, Mexico City, Mexico.
Published: January 2005
Angiotensin (ANG) II can be associated with gene expression regulation. Thus we studied the possible role of ANG II in the regulation of AT(2) 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 AT(1) receptor antagonist losartan, or the AT(2) receptor antagonist PD-123319. Renal tissue was analyzed for histological changes and expression of AT(2) receptor mRNA (by RT-PCR) and protein (by immunohistochemistry). To explore the physiological role of AT(2) 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 AT(2) 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 AT(2) receptor expression, whereas the losartan-pretreated group showed a further increase in AT(2) receptor expression. Inhibition of the AT(2) receptor during renal ablation was associated with increased renal damage and a further increase in the blood pressure. This suggests that overexpression of AT(2) receptors after renal ablation is modulated by ANG II through its own AT(2) receptor and that functional expression of this effect may represent a counterregulatory mechanism to modulate the renal damage induced by renal ablation.
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Wolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. Electronic address:
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Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq.
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