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(Hypertension. 2000;35:480.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Gender Differences in Development of Hypertension in Spontaneously Hypertensive Rats
Role of the Renin-Angiotensin System
From the Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson.
Correspondence to Jane F. Reckelhoff, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State St, Jackson, MS 39216-4505. E-mail Jreckelhoff{at}physiology.umsmed.edu
Abstract—Previous data strongly support a role for androgens in promoting the gender difference in hypertension in the spontaneously hypertensive rat(s) (SHR), but the mechanism is not clear. Because males develop higher blood pressures than do females, we hypothesize that androgens may affect the renin-angiotensin system to promote the development of hypertension in male SHR. The present study was performed to determine the effect of converting enzyme inhibition (CEI) on the development of hypertension in SHR. Male, female, castrated male, and ovariectomized (ovx) female SHR (n=10 per gender per treatment group) received enalapril (250 mg/L) in drinking water for 8 to 10 weeks. Some ovx females were also given testosterone chronically. At 17 to 19 weeks of age, 24-hour protein excretion and mean arterial pressure were measured. By 13 weeks of age, male rats had higher systolic blood pressures by tail plethysmography than did the other rats, and CEI reduced blood pressures to similar levels in all groups. At 17 to 19 weeks, the same trend was found by direct measurement of mean arterial pressure. The ovx females treated with testosterone had serum testosterone and blood pressure levels similar to those found in males. CEI reduced mean arterial pressure to similar levels in all gender groups. Untreated males and ovx females given testosterone had significantly higher levels of urinary protein excretion than did the other groups, and CEI had no effect on proteinuria in any of the rats. These data suggest that the development of hypertension in SHR regardless of sex steroids is mediated by the renin-angiotensin system. However, the data further suggest that androgens promote the exacerbation of hypertension in male SHR via a mechanism involving the renin-angiotensin system.
Key Words: gender • renin-angiotensin system • angiotensin-converting enzyme • testosterone
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