Sex-Specific Effect of Endothelin in the Blood Pressure Response to Acute Angiotensin II in Growth-Restricted Rats [Endothelin and Intrauterine Growth Restriction]

The renal endothelin system contributes to sex differences in blood pressure with males demonstrating greater endothelin type-A receptor-mediated responses relative to females. Intrauterine growth restriction programs hypertension and enhance renal sensitivity to acute angiotensin II in male growth-restricted rats. Endothelin is reported to work synergistically with angiotensin II. Thus, this study tested the hypothesis that endothelin augments the blood pressure response to acute angiotensin II in male growth-restricted rats. Systemic and renal hemodynamics were determined in response to acute angiotensin II (100 mg/kg per minute for 30 minutes) with and without the endothelin type-A receptor antagonist, Atrasentan (ABT-627; 10 ng/kg per minute for 30 minutes), in rats pretreated with enalapril (250 mg/L for 1 week) to normalize the endogenous renin–angiotensin system. Endothelin type-A receptor blockade reduced angiotensin II–mediated increases in blood pressure in male control and male growth-restricted rats. Endothelin type-A receptor blockade also abolished hyper-responsiveness to acute angiotensin II in male growth-restricted rats. Yet, blood pressure remained significantly elevated above baseline after endothelin type-A receptor blockade, suggesting that factors in addition to endothelin contribute to the basic angiotensin II–induced pressor response in male rats. We also determined sex-specific effects of endothelin on acute angiotensin II–medi...
Source: Hypertension - Category: Cardiology Authors: Tags: Animal Models of Human Disease, Basic Science Research, Hypertension Endothelin and Intrauterine Growth Restriction Source Type: research