Endothelin and blood pressure regulation in the female rat: Studies in normal pregnancy and with nitric oxide synthase inhibition-induced hypertension

Objective: To evaluate the role of endothelin (ET) in blood pressure regulation in normal pregnant and nonpregnant rats and with nitric oxide synthase (NOS) inhibition. Methods: Pregnant and nonpregnant Sprague-Dawley rats were treated for 7 days with an ETA-selective (A-127722 or FR-139317), ETB-selective (A-192621), or ETA/ETB nonselective (A-182086) endothelin receptor antagonist, and/or with the NOS inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg/h). In pregnant rats, the ET antagonists and L-NAME were administered from gestational day 14 through day 21 (term = 22 days). All rats received indwelling arterial catheters for blood pressure measurement. Mean arterial pressures were recorded on infusion days 1, 4, and 7 and these data were compared by analysis of variance among experimental groups with p < 0.05 considered significant. Results: The ETA receptor antagonism lowered blood pressure in both pregnant and nonpregnant rats (p < 0.05), whereas ETB antagonism resulted in hypertension (p < 0.001). ETB antagonism-induced hypertension was attenuated by pregnancy (p < 0.001). Hypertension was induced in all rats treated with L-NAME (p < 0.001). Endothelin receptor antagonism, regardless of specificity, did not ameliorate L-NAME-induced hypertension in pregnant or nonpregnant female rats. The only observed effect of ETA antagonism on NOS inhibition induced hypertension was the prevention of a continued rise at infusion day 7 in nonpregnant rats. Conclusions: Endothelin, acting via both the ETA and ETB receptors, contributes to blood pressure homeostasis in pregnant and nonpregnant rats. Endothelin receptor antagonism does not ameliorate NOS-inhibition-induced hypertension in pregnant rats.