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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H1184    most recent 01114.2008v1 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 Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Ferrario, C. M. Articles by Sowers, J. R. Search for Related Content PubMed PubMed Citation Articles by Ferrario, C. M. Articles by Sowers, J. R.

Differential regulation of angiotensin-(1-12) in plasma and cardiac tissue in response to bilateral nephrectomy

¹Hypertension and Vascular Research Center and Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina; ²Diabetes Cardiovascular Center, University of Missouri-Columbia School of Medicine, and Harry S. Truman VA Medical Center, Columbia, Missouri; and ³Circulatory and Body Fluid Regulation, Faculty of Medicine University of Miyazaki, Kihara, Kiyotake, Miyazaki, Japan

Submitted 22 October 2008 ; accepted in final form 9 February 2009

We examined the effects of 48 h bilateral nephrectomy on plasma and cardiac tissue expression of angiotensin-(1-12) [ANG-(1-12)], ANG I, and ANG II in adult Wistar-Kyoto rats to evaluate functional changes induced by removing renal renin. The goal was to expand the evidence of ANG-(1-12) being an alternate renin-independent, angiotensin-forming substrate. Nephrectomy yielded divergent effects on circulating and cardiac angiotensins. Significant decreases in plasma ANG-(1-12), ANG I, and ANG II levels postnephrectomy accompanied increases in cardiac ANG-(1-12), ANG I, and ANG II concentrations compared with controls. Plasma ANG-(1-12) decreased 34% following nephrectomy, which accompanied 78 and 66% decreases in plasma ANG I and ANG II, respectively (P < 0.05 vs. controls). Contrastingly, cardiac ANG-(1-12) in anephric rats averaged 276 ± 24 fmol/mg compared with 144 ± 20 fmol/mg in controls (P < 0.005). Cardiac ANG I and ANG II values were 300 ± 15 and 62 ± 7 fmol/mg, respectively, in anephric rats compared with 172 ± 8 fmol/mg for ANG I and 42 ± 4 fmol/mg for ANG II in controls (P < 0.001). Quantitative immunofluorescence revealed significant increases in average grayscale density for cardiac tissue angiotensinogen, ANG I, ANG II, and AT₁ receptors of WKY rats postnephrectomy. Faint staining of cardiac renin, unchanged by nephrectomy, was associated with an 80% decrease in cardiac renin mRNA. These changes were accompanied by significant increases in p47^phox, Rac1, and Nox4 isoform expression. In conclusion, ANG-(1-12) may be a functional precursor for angiotensin peptide formation in the absence of circulating renin.

renin; angiotensinogen; angiotensin II; blood pressure