Published online before print November 10, 2003, doi: 10.1161/01.HYP.0000102180.13341.50
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(Hypertension. 2003;42:1157.)
© 2003 American Heart Association, Inc.
Scientific Contributions |
Postovariectomy Hypertension Is Linked to Increased Renal AT1 Receptor and Salt Sensitivity
From the Department of Physiology, Tulane University Health Sciences Center (L.M.H.-B.), New Orleans, La; and Renal Division, VA Medical Center and Vascular Biology Institute, University of Miami (I.H.S., L.R.), Miami, Fla.
Correspondence to Lisa M. Harrison-Bernard, PhD, Department of Physiology, SL39 Tulane University Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112-2699. E-mail lharris{at}tulane.edu
The functional balance between angiotensin II (Ang II) and nitric oxide (NO) plays a key role in modulating salt sensitivity. Estrogen has been shown to downregulate angiotensin type 1 (AT1) receptor expression and to increase the bioavailability of endothelium-derived NO, which decreases AT1 receptor expression. The present study tests the hypothesis that in the presence of genetic salt sensitivity, deficiency of endogenous estrogens after ovariectomy (OVX) fosters an upregulation of Ang II. Female Dahl salt-resistant (DR), Dahl salt-sensitive (DS), Wistar-Kyoto (WKY), and spontaneously hypertensive (SHR) rats underwent bilateral OVX or sham surgery (SHX) and were fed a normal salt diet (0.5% NaCl) for 14 weeks. Systolic blood pressures were measured every 2 weeks and were not significantly different between OVX and SHX for DR, WKY, and SHR groups. However, at the end of 14 weeks of normal salt diet, hypertension developed in DS OVX but not SHX rats (160±3 versus 136±3 mm Hg; P<0.05). Hypertension also developed in DS OVX rats pair-fed a normal salt diet (166±7 mm Hg). Development of hypertension in DS OVX rats was prevented by estrogen replacement (132±3 mm Hg), AT1 receptor blockade (119±3 mm Hg), or feeding a very low salt diet (0.1% NaCl; 129±4 mm Hg). Renal AT1 receptor protein expression was significantly elevated 2-fold in DS OVX relative to SHX rats and was prevented by estrogen replacement. These data strongly suggest that after OVX in salt-sensitive rats there is a lower threshold for the hypertensinogenic effect of salt that is linked to an activation of Ang II.
Key Words: rats, Dahl • rats, spontaneously hypertensive • sodium, dietary • angiotensin II • estrogen • receptors, angiotensin
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