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pubmed-article:19075092pubmed:abstractTextIn Sprague-Dawley rats, renal angiotensin (Ang) type 2 receptors (AT(2)Rs) mediate natriuresis in response to renal interstitial (RI) D(1)-like receptor stimulation or RI Ang III infusion. After D(1)-like receptor activation, apical membrane (AM) but not total renal proximal tubule cell AT(2)R expression is increased, suggesting that AM AT(2)R translocation may be important for natriuresis. The onset of hypertension in spontaneously hypertensive rats (SHRs) is preceded by defects in renal sodium excretion. The present study examines AT(2)R-mediated natriuresis in response to RI Ang III infusion in Wistar-Kyoto rats (WKYs) and SHRs. WKYs and SHRs received RI Ang III infusion after 24 hours of systemic AT(1)R blockade with candesartan. In WKYs, urine sodium excretion rate increased from 0.043+/-0.01 to 0.191+/-0.06 micromol/min (P<0.05) in response to Ang III infusion, but identical conditions failed to increase the urine sodium excretion rate in SHRs. The increase in the urine sodium excretion rate was blocked by coinfusion of PD-123319, a selective AT(2)R antagonist. On confocal microscopy images, Ang III-infused WKYs demonstrated greater renal proximal tubule cell AM AT(2)R fluorescence intensity compared with SHRs (5385+/-725 versus 919+/-35; P<0.0001), and Western blot analysis demonstrated increased AM (0.050+/-0.003 versus 0.038+/-0.003; P<0.01) but not total cell AT(2)R expression in WKYs. In SHRs, AM AT(2)R expression remained unchanged in response to RI Ang III infusion. Thus, RI Ang III infusion elicits natriuresis and renal proximal tubule cell AT(2)R translocation in WKYs. Identical manipulations fail to induce natriuresis or AT(2)R translocation in SHRs, suggesting that defects in AT(2)R-mediated natriuresis and trafficking may be important to the development of hypertension in SHRs.lld:pubmed
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pubmed-article:19075092pubmed:articleTitleIntrarenal angiotensin III infusion induces natriuresis and angiotensin type 2 receptor translocation in Wistar-Kyoto but not in spontaneously hypertensive rats.lld:pubmed
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