Mechanisms of central endothelin-induced hypotension.

The aims of the present study were i) to determine the type of endothelin receptor(s) mediating the hypotension produced by central administration of endothelin-1 (ET-1), ii) to delineate the hemodynamic factors contributing to this hypotension and iii) to differentiate between the neural and cerebrovascular actions of ET-1. Towards these objectives, we monitoreal blood flow from the choroid plexus of the IVth cerebral ventricle (4CV) as an index of local cerebral blood flow (CBF); also, aortic blood flow (ABF) and cutaneous microvascular blood flow (CMF) of the hindpaw were monitored. In anesthetized, ventilated rats, ET-1 (1, 3 and 10 pmol) applied to the 4CV produced significant decreases in mean arterial blood pressure (15 +/- 4%, 34 +/- 3% and 37 +/- 3% respectively); hypotension was sustained at the two higher doses. ET-1 also produced a profound and sustained reduction in CBF (36 +/- 10%, 54 +/- 10% and 57 +/- 11% respectively). Prior administration of a low dose (1 nmol) of the ETA receptor selective antagonist, BQ-123 [cyclo (D-Trp-D-Asp-L-Pro-D-Val-L-Leu)], abolished only the central ET-1-induced hypotension; the decreases in CBF were not altered (57 +/- 11% and 56 +/- 6% respectively after 3 and 10 pmol). Pretreatment with a high dose (20 nmol) of BQ-123 attenuated but did not abolish the CBF response to 10 pmol of ET-1 (-26 +/- 1% vs. -57 +/- 11%).(ABSTRACT TRUNCATED AT 250 WORDS)