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1 Center for the Study of Sex Differences, Georgetown University, Washington, DC, USA; Physiology & Biophysics, Georgetown University, Washington, DC, USA
2 DISTBIMO, University of Genova, Genova, Italy
3 Center for the Study of Sex Differences, Georgetown University, Washington, DC, USA; Medicine, Georgetown University, Washington, DC, USA
4 Pharmacology, Michigan State University, East Lansing, MI, USA
* To whom correspondence should be addressed. E-mail: jih{at}georgetown.edu.
To investigate the faster rate of renal disease progression in men compared to women, we addressed the following questions in the renal wrap (RW) model of hypertension: 1) Do sex differences exist in RW-induced renal injury, which are independent of sex differences in blood pressure? 2) Are their sex-differences in nitric oxide (NO) production in RW hypertension? Male (M) and female (F) rats underwent sham (M-Sham, n=7; F-Sham, n=10) or RW (M-RW, n=13; F-RW, n=14) surgery for 9 weeks. Markers of renal injury including the glomerulosclerosis index (GSI: F-RW, 0.70 ± 0.1 vs M-RW, 2.2 ± 0.6, p<0.05), mean glomerular volume (F-RW, 1.05±0.050x106 vs M-RW, 1.78±0.15x106 µm3; p<0.001) and proteinuria (F-RW, 68.7±15 vs M-RW, 124±7.7 mg/day; p<0.001) were greater in RW males compared to RW females. Endothelial nitric oxide synthase (eNOS) protein expression was elevated in the renal cortex (3.2-fold) and medulla (2.2-fold) 9 weeks after RW in males whereas no differences were observed in females. Neuronal NOS (nNOS) protein expression was unchanged in the renal cortex in males and in both the renal cortex and medulla in females, whereas in the male medulla, nNOS was decreased by 57%. These data suggest the degree of renal injury is greater in male compared to female rats in RW hypertension despite similar degrees of hypertension and renal function and may involve sex differences in renal NO metabolism.
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