Gonadal steroid regulation of renal injury in renal wrap hypertension

Renal injury is greater in male compared with female rats after renal wrap (RW) hypertension. We investigated the role of gonadal steroids in the sex differences in RW disease severity in male (M) and female (F), castrated (Cast), and ovariectomized (OVX) rats and after dihydrotestosterone (DHT) and 17beta-estradiol (E2) treatment. Male castration attenuated the severity of RW-induced glomerulosclerosis (GS) [GS index (GSI): RW-M, 2.1 +/- 0.2; RW-Cast, 1.3 +/- 0.2; RW-Cast+DHT, 2.4 +/- 0.4], mean glomerular volume (MGV; microm3 x 10(6): RW-M, 1.9 +/- 0.1; RW-Cast, 1.45 +/- 0.15; RW-Cast+DHT, 1.91 +/- 0.15), tubular damage, and proteinuria (mg/day: RW-M, 130 +/- 8; RW-Cast, 105 +/- 5; RW-Cast+DHT, 142 +/- 9), whereas DHT treatment abrogated these effects. Ovariectomy increased the GSI (RW-F, 0.69 +/- 0.05; RW-OVX, 1.2 +/- 0.1; RW-OVX+E2, 0.65 +/- 0.05), tubular damage, and MGV (microm3 x 10(6): RW-F, 1.0 +/- 0.06; RW-OVX, 1.5 +/- 0.05; RW-OVX+E2, 0.96 +/- 0.06), whereas E2 treatment prevented these effects. Furthermore, DHT treatment of RW-OVX animals exacerbated the GSI (1.9 +/- 0.19), MGV (1.7 +/- 0.2 x 10(6) microm3), and proteinuria (171 +/- 21 mg/day) even further. Our data show that the lack of E2 and presence of androgens contribute to progressive renal disease induced by RW hypertension, suggesting that gonadal steroid status is an independent factor in the greater susceptibility men exhibit toward hypertension-associated renal disease compared with women.