Abstract 9: Endothelin B Receptors Protect Against Hypertension Induced by Chronic Angiotensin II in Female Rats

Endothelin B (ET B ) receptors mediate vasodilation, anti-inflammation and natriuresis, which ultimately contribute to blood pressure control. We previously showed that renal medullary ET B receptor function is maintained in female angiotensin (Ang) II hypertensive rats, while male Ang II hypertensive rats have blunted ET B -induced natriuretic responses. Because female rats are more resistance to blood pressure elevation induced by high salt intake and/or Ang II infusion, we hypothesized that ET B receptors protect female rats against the hypertensive response and renal injury induced by a high salt diet and chronic Ang II infusion compared to males. Male and female rats received Ang II infusion (150 ng/kg/min; sc.) with 4% NaCl for 4 weeks; blood pressure was measured by telemetry. After a week of Ang II infusion with a high salt diet, subsets of both male and female rats received the ET B antagonist, A-192621, at three doses on consecutive weeks (1, 3, and 10 mg/kg/d in food). Male rats had a significantly higher blood pressure compared to females after 4 weeks of Ang II (178±10 vs. 138±10 mmHg; p<0.05). A-192621 resulted in a dose-dependent increase in blood pressure in female Ang II hypertensive rats (167±8 mmHg at 10 mg/kg/d; p<0.05); the increase produced by A-192621 in male Ang II hypertensive rats was not statistically significant (193±10 mmHg). After 4 weeks of Ang II infusion, the level of proteinuria and nephrinuria was higher in male rats compared to female. A-192621 did not further increase urinary excretion of protein or nephrin in both male and female Ang II hypertensive rats. In conclusion, these results support the hypothesis that ET B receptors provide more protection against hypertension during chronic Ang II infusion in female rats compared to male.