Blood pressure responses to intravenous or intracerebroventricular endothelin-1 in spontaneously hypertensive rats.

Responses of blood pressure to intravenous (i.v.) or intracerebroventricular (i.c.v.) endothelin-1 (ET-1) in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were investigated. Conscious male SHRs and WKY rats were used for the experiments. ET-1 (300-1,000 ng/kg) was injected intravenously in the i.v. experiments, or 30 and 100 ng/kg of ET-1 were injected into the lateral ventricle in the i.c.v. experiments. The initial depressor response to i.v. ET-1 was greater in SHRs (n = 10) than in WKY rats (n = 10) at 1,000 ng/kg (-54 +/- 6 vs. -41 +/- 3 mm Hg, mean +/- SEM, p less than 0.05). The subsequent pressor response to i.v. ET-1 was smaller in SHRs than in WKY rats (3.5 +/- 0.8 vs. 7.0 +/- 0.9 mm Hg at 300 ng/kg, p less than 0.05, and 11 +/- 2 vs. 17 +/- 2 mm Hg at 1,000 ng/kg, p less than 0.05). Pressor responses to i.c.v. ET-1 were not different in SHRs (n = 8) and WKY rats (n = 8) at both doses (10 +/- 4 vs. 10 +/- 3 mm Hg at 30 ng/kg, and 46 +/- 10 vs. 49 +/- 10 mm Hg at 100 ng/kg). A greater initial depressor response and a smaller subsequent pressor response to i.v. ET-1 were observed in SHRs than in WKY rats. The attenuated pressor response to intravenously administered ET-1 may be unique since vasoconstrictor responses to other known vasoactive substances such as angiotensin, catecholamines, or vasopressin are reportedly augmented in SHRs. We did not find any difference in responsiveness to i.c.v. ET-1 between SHRs and WKY rats.