Chronic Synergistic Effect of Endothelin-1 and Angiotensin II on blood pressure in conscious rats

We assessed whether there is an interaction between angiotensin II (Ang II) and endothelin-1 (ET-1) in the regulation of blood pressure and sodium and water metabolism in rats. Male Sprague-Dawley rats were divided into four groups. Group I rats received Ang II at a subpressor dose (400 μg/kg/day i.p.) for up to 6 days. Group II rats received ET-1 at a subpressor dose (3 μg/kg/day i.v.) for up to 6 days. Group III rats received both the subpressor dose of Ang II and the subpressor dose of ET-1. Group IV rats received vehicle only. There was no significant difference in systolic blood pressure (SBP) among groups I, II, and IV during the study. On day 6. SBP in groups I, II, and IV was 148.0 ± 3.0, 142.7 ± 2.9. and 143.5 ± 3.0 mm Hg, respectively. On the other hand, SBP in group III was higher than those of the other groups on day 2 and remained elevated thereafter. On day 6. SBP in group III rats was 189.0 ± 12.5 mm Hg. There were no significant differences in body weight, fluid intake, urine volume, urinary sodium excretion, or urinary potassium excretion among the four groups. The present results suggest that Ang II and ET-1 exert their pressor effects synergistically and might play a role in controlling blood pressure. They also suggest the possibility of the existence of a common pathway in the hypertension-producing mechanism of these two peptides.