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Am J Physiol Renal Physiol (January 10, 2006). doi:10.1152/ajprenal.00317.2005
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Submitted on August 5, 2005
Accepted on December 30, 2005

DIFFENTIAL EXPRESSION OF NUCLEAR AT1 RECEPTORS AND ANGIOTENSIN II WITHIIN THE KIDNEY OF THE MALE CONGENIC mREN2.LEWIS RAT

Karl D. Pendergrass1, David B. Averill1, Carlos M. Ferrario1, Debra I. Diz1, and Mark C. Chappell1*

1 The Hypertension and Vascular Disease Center, Winston-Salem, NC, USA

* To whom correspondence should be addressed. E-mail: mchappel{at}wfubmc.edu.

We established a new congenic model of hypertension, the mRen(2).Lewis rat and assessed the intracellular expression of angiotensin peptides and receptors in the kidney. The congenic strain was established from the backcross of the (mRen2)27 transgenic rat that expresses the mouse renin 2 gene onto the Lewis strain. The 20 week old male congenic rats were markedly hypertensive as compared to the Lewis controls [systolic blood pressure: 195 ± 2 versus 107 ± 2 mmHg, p < 0.01]. Although plasma Ang II levels were not different between strains, circulating levels of Ang-(1-7) were 270% higher and Ang I concentrations were 40% lower in the mRen2.Lewis rats. In contrast, both cortical (CORT) and medullary (MED) Ang II concentrations were 60% higher in the mRen2.Lewis rats, while tissue Ang I was 66% and 84% lower in CORT and MED. For both strains, MED Ang II, Ang I and Ang-(1-7) were significantly higher than CORT levels. Intracellular Ang II binding distinguished nuclear (NUC) and plasma membrane (PM) receptor using the Ang II radioligand 125I-Sarthran. Isolated CORT nuclei exhibited a high density (Bmax >200 fmol/mg protein) and affinity for the Sarthran ligand (KD<0.5 nM), the majority of these sites (>95%) were the AT1 receptor subtype. CORT Ang II receptor Bmax and KD values in nuclei were 75% and 50% lower, respectively, for the mRen(2).Lewis versus the Lewis rats. In the MED, the PM receptor density [Lewis: 50 ± 4 versus mRen2.Lewis: 21 ± 5 fmol/mg protein) and affinity [KD: Lewis: 0.31 ± 0.1 versus 0.69 ± 0.1 nM] were lower in the mRen2.Lewis. In summary, the hypertensive mRen2.Lewis rats exhibit higher Ang II in both CORT and MED regions of the kidney. Evaluation of intracellular Ang II receptors revealed lower CORT NUC and MED PM AT1 sites in the mRen2.Lewis. The down-regulation of AT1 sites in the mRen2.Lewis may reflect a compensatory response to dampen the elevated levels of intrarenal Ang II.




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