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Department of Nephrology and Hypertension, University Hospital Utrecht, 3508 GA Utrecht, The Netherlands
Men are at greater
risk for renal injury than women. We studied whether male rats are more
sensitive to the hypertensive and proteinuric effects of chronic nitric
oxide sythase (NOS) inhibition than female rats. In addition, we
studied whether androgens or estrogens are responsible for differences
in sensitivity to proteinuria induced by chronic NOS inhibition.
Females and males were treated with 10, 20, 30, and 100 mg/l
N
-nitro-L-arginine
(L-NNA) during 24 wk. Systolic blood pressure (SBP) and
proteinuria were measured regularly and compared with time-control
measurements in control females and males. In females and males
treatment with 10 mg/l L-NNA had no effect on SBP or proteinuria. Treatment with 20, 30, and 100 mg/l L-NNA
resulted in a dose-dependent increase in SBP that was similar in males and females. However, females treated with 20 and 30 mg/l
L-NNA were resistant to the development of proteinuria:
maximum values were 16 ± 7 and 46 ± 21, respectively, vs.
16 ± 3 mg/day in controls, whereas males treated with those doses
showed an increase in proteinuria [139 ± 35 (P < 0.05) and 318 ± 82 (P < 0.01), respectively,
vs. 55 ± 11 mg/day in controls]. Treatment with 100 mg/l
L-NNA increased proteinuria similarly in both females and
males. To study the role of sex hormones in differences in sensitivity
to proteinuria induced by mild chronic NOS inhibition, treatment with
20 mg/l L-NNA was repeated in ovariectomized (Ovx) and
orchidectomized rats. Ovariectomy did not affect the increase in SBP
caused by 20 mg/l L-NNA, but, in contrast to intact
females, this dose of L-NNA did cause Ovx rats to develop
proteinuria (51 ± 16 vs. 16 ± 7 mg/day in control Ovx rats;
P < 0.05). Orchidectomy completely prevented the
increased SBP as well as proteinuria induced by 20 mg/l
L-NNA in male rats. In conclusion, male rats are more sensitive than female rats to develop proteinuria induced by mild chronic NOS inhibition. Estrogens provide some protection in females, whereas androgens are responsible for the increased sensitivity of male
rats to proteinuria induced by mild chronic NOS inhibition. Risk
factors associated with a compromised nitric oxide system may be more
detrimental to the kidney in men than in women.
nitric oxide synthase; systolic blood pressure; gonadectomy; estrogens; androgens
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