Sex‐specific mechanisms contribute to the pressor response to acute angiotensin II in a rat model of intrauterine growth restriction

Abstract

When the endogenous renin angiotensin system (RAS) is blocked by enalapril, male and female rats exhibit a pressor response to acute angiotensin II (Ang II). Endothelin contributes to the pressor response to acute AngII in male rats; yet the importance of endothelin in female rats is unknown. Moreover, hypersensitivity to acute Ang II in male intrauterine growth restricted (IUGR) rats is abolished by endothelin type A receptor (ETAR) blockade. Thus, we tested the hypothesis that endothelin plays a key role in mediating the pressor response to acute Ang II in female rats. Mean arterial pressure (MAP) was measured in conscious, chronically instrumented female control and female IUGR rats pretreated with enalapril (250 mg/L) for 1 week. MAP was measured for 30 minutes before or after an acute infusion of Ang II (100 ng/kg/min), and plus or minus ETAR blockade (ABT627, 10 mg/kg/min). MAP was increased in response to acute Ang II in female control and female IUGR rats; however, ETAR blockade had no effect on blood pressure in Ang II treated female rats, control or IUGR. Thus, these data indicate that the blood pressure response to acute Ang II does not involve endothelin in female rats. Importantly, this study highlights that sex-specific mechanisms contribute to the acute pressor response to Ang II. MAP (mmHg) Baseline Ang II Ang II + ETARB Female Control 110±3 140±4* 145±5* Female IUGR 111±2 141±1* 139±6* * P < 0.001 vs. Baseline