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(Hypertension. 1999;34:920-923.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Gender Differences in Hypertension in Spontaneously Hypertensive Rats
Role of Androgens and Androgen Receptor
From the Department of Physiology and Biophysics, The Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Miss.
Correspondence to Jane F. Reckelhoff, PhD, Associate Professor, Physiology and Biophysics, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. E-mail JReckelhoff{at}physiology.umsmed.edu
Abstract—Males are at greater
risk of cardiovascular and renal disease than are
females. For example, male spontaneously hypertensive rats (SHR) have
higher blood pressures than females. Androgens have been strongly
implicated in the hypertension of male SHR, because castration
attenuates the hypertension. This study determined whether the androgen
receptor plays a role in hypertension in male SHR and whether
testosterone alone can cause the hypertension or whether conversion to
dihydrotestosterone is necessary. Male SHR, aged 10 weeks, were given
the androgen receptor antagonist flutamide (8 mg/kg SC;
n=8) or the 5
-reductase inhibitor finasteride (30
mg · kg-1 · d-1 SC; n=11) daily
for 5 to 6 weeks. Control rats (n=10) received vehicle (20% benzyl
benzoate or ethanol in castor oil). After 5 to 6 weeks, blood pressure
(mean arterial pressure) and glomerular
filtration rate were measured. Long-term flutamide treatment caused a
reduction in mean arterial pressure (control 178±5
mm Hg; flutamide 159±3 mm Hg; P<0.01), but
finasteride had no effect (180±5 mm Hg). There were no
differences in glomerular filtration rate among the groups.
These data indicate that hypertension in male SHR is mediated via the
androgen receptor and does not require conversion of testosterone
to dihydrotestosterone.
Key Words: flutamide • finasteride • blood pressure • gender
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