These findings indicate that sexual dimorphism exists in remnant kidney growth and function two months following UNX. Indeed, morphological abnormalities and impairment in renal phosphate handling are affected by gonadal steroids by two-months post-UNX. The fact that renal Pi transport was reduced in female but not male UNX rats may also have important implications during periods of high metabolic demand for phosphate in the female.

Although the mechanisms are not understood, evidence suggests that 17beta-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E2 decreases angiotensin type 1 receptors (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx +/- E2; Cas +/- DHT) for 3 wk. Cortical ERalpha protein was 2.5 times greater, and ERbeta was 80% less in females vs. males (P < 0.01). Glomerular AT1R binding was lower in females than males [4,657 +/- 838 vs. 7,457 +/- 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERalpha protein by 50%, whereas E2 increased ERalpha expression after Ovx. The decrease in cortical ERalpha in Ovx rats was associated with a significant increase in AT1R binding (6,908 +/- 609 cpm), and E2 prevented this increase. There was no change in ERalpha or AT1R binding following Cas +/- DHT (25 mg) treatment, although Cas did elevate cortical ERbeta (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERalpha 150% above intact levels and profoundly decreased AT1R binding (1,824 +/- 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ERalpha and is inversely associated with glomerular AT1R binding, supporting our hypothesis that E2 tonically suppresses AT1Rs and suggesting a potential mechanism for the protective effects of estrogen.

This study demonstrates that despite a significant attenuation in the NO-related renal vasodilatory responses, the integrity of the renal NO system is preserved in rats with chronic AV fistula. This impairment in NO-mediated renal vasodilation in experimental CHF appears to be related to increased activity of the renin-angiotensin system and may contribute further to the decrease in renal perfusion seen in CHF.