Abstract P248: Estrogen Replacement Mitigated Blood Pressure Elevation Via Suppression Of Sodium Cotransporter In Angiotensin Ii-infused Ovariectomized Female Rats

Abstract

Introduction: Female rats with lower proximal sodium transporters are known to excrete natriuresis faster than male rats. However, it is not sure whether the protective effect would be conserved in menopausal rats. Hypothesis: We assessed the hypothesis that ovariectomy would change renal sodium transporters in female rats and the estrogen supplementation could reverse angiotensin II (ANGII)-induced changes in renal sodium transporters and natriuresis. Methods: Six-week female Sprague Dawley rats (n=22) were ovariectomized, and half of them (n=11) were treated with estradiol 2 weeks later for 4 weeks, and then ANGII (n=14) or vehicle (n=8) was infused via osmotic minipumps for 2 weeks. Blood pressure (BP) was measured by the tail-cuff sphygmomanometer. Blood, urine, and kidney samples were collected. Results: The ANGII induced significant BP elevation in ovariectomized (OVX) and OVX with estradiol (OVX+E) rats. OVX affected elevating BP even in the sham rats. Albuminuria significantly increased in ANGII-infused OVX rats and did not change in ANGII-infused OVX+E rats. Urine sodium was significantly decreased in ANGII-infused OVX rats, while it increased in ANGII-infused OVX+E rats. Sodium transporters in the proximal tubule (sodium-hydrogen exchange 3, sodium phosphate cotransporter) were not different between OVX and OVX+E irrespective of ANGII infusion. Among the distal tubule transporters (α/β/γ-epithelial sodium channel (α/β/γENaC), sodium chloride cotransporter (NCC), phosphorylated NCC (pNCC)), pNCC were markedly augmented in ANGII-infused OVX rats, whereas not changed in ANGII-infused OVX+E rats. ANGII infusion affected increasing ANGII type 2 receptor (AT 2 R) in OVX+E rats but did not influence AT 2 R levels in OVX rats. Conclusions: Estradiol has the protective effect from elevating BP in ANGII-infused OVX rats. It was achieved via augmentation of natriuresis, which was connected to the suppression of NCC.