on February 7, 2008
Published online before print February 7, 2008, doi: 10.1161/HYPERTENSIONAHA.107.100750
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Submitted on August 31, 2007
From the Department of Physiology, School of Medicine, Aging Institute, University of Murcia, Murcia, Spain. * To whom correspondence should be addressed. E-mail: salazar{at}um.es.
Abstract—We have demonstrated that the reduction of angiotensin II effects during the nephrogenic period reduces the nephron number and induces the development of hypertension. The hypotheses examined are that this reduction of angiotensin effects leads to the development of an age-dependent sodium sensitive hypertension and that the hypertension is angiotensin II dependent. Newborn rats were treated with an angiotensin II type 1 receptor antagonist during the first 2 weeks of age. At 3 to 4 and 11 to 12 months of age, changes in systolic blood pressure, proteinuria, and renal function in response to a prolonged high sodium intake were examined. The basal blood pressure response to the administration of the angiotensin II receptor antagonist was also evaluated at both ages. Basal blood pressure was similarly elevated (P<0.05) in male and female treated rats, and the increment was age dependent. High sodium intake only elicited a blood pressure elevation (136±1 to 154±3 mm Hg; P<0.05) and a decrease in glomerular filtration rate (28%; P<0.05) at 11 to 12 months in treated rats. Blockade of angiotensin II receptors during renal development induced an increase (P<0.05) in proteinuria that was age and sex dependent, but high sodium intake only induced an elevation in proteinuria in the younger rats (50%; P<0.05). Hypertension was maintained by angiotensin II at both ages because blood pressure decreased to normal levels after treatment with an angiotensin II type 1 receptor antagonist. This study shows that the reduction of angiotensin II effects during the nephrogenic period modifies renal function and induces the development of an angiotensin II–dependent hypertension that becomes sodium sensitive during aging.
Revised on October 8, 2007
Age- and Sodium-Sensitive Hypertension and Sex-Dependent Renal Changes in Rats With a Reduced Nephron Number
Francisco Salazar;
Key words: angiotensin II • renal function • nephrogenesis • proteinuria
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Hypertension 2008 51: 997-999.
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