The present study was undertaken to determine whether sex hormones inf
luence nitric oxide synthase levels in the kidney. Five groups of rats
were studied: males, castrated males, females, oophorectomized female
s, and oophorectomized females receiving estradiol replacement therapy
. Endothelial nitric oxide synthase (eNOS) levels in the kidney were m
easured by Western blotting. eNOS levels were significantly greater in
the renal medulla of female rats compared with male rats (3545 +/- 47
3 versus 2418 +/- 205 densitometry units (DU), P < 0.05). Oophorectomy
reduced renal medullary eNOS levels to that of intact male rats (2566
+/- 304 DU, P = NS). Estrogen replacement therapy significantly incre
ased medullary eNOS levels in oophorectomized animals (3249 +/- 377 ve
rsus 2302 +/- 213 DU, P < 0.05). Renal inducible nitric oxide synthase
(iNOS) levels were measured after induction with lipopolysaccharide.
iNOS levels were significantly greater in the renal medulla of female
rats compared with male rats (677 +/- 253 versus 252 +/- 12 DU, P < 0.
05). Oophorectomy reduced renal medullary iNOS levels to that of intac
t male rats (295 +/- 57 DU, P = NS). In contrast, estrogen replacement
therapy significantly increased medullary iNOS levels in oophorectomi
zed animals (682 +/- 356 versus 160 +/- 92 DU, P < 0.05). Steady-state
levels of mRNA for NOS were found to be higher in the inner medulla o
f female rats compared with male rats (1519 +/- 211 versus 899 +/- 105
DU, P < 0.05). In contrast to these findings, sex hormones failed to
influence nitric oxide production or iNOS levels in lipopolysaccharide
-stimulated mesangial cells in culture. These results suggest that gen
der may influence renal medullary synthesis of nitric oxide.