SEX-HORMONES AND RENAL NITRIC-OXIDE SYNTHASES

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.