Winquist R J, Bunting P B, Garsky V M, Lumma P K, Schofield T L
Department of Pharmacology, Merck, Sharp & Dohme Research Laboratories, West Point, PA 19486.
Eur J Pharmacol. 1989 Apr 12;163(1):199-203. doi: 10.1016/0014-2999(89)90420-2.
Administration of endothelin (0.03-3.0 micrograms/kg i.v.) caused transient depressor responses followed by sustained pressor responses in anesthetized spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The initial depressor response occurred at lower doses (0.1 versus 0.3 micrograms/kg i.v.) in SHR versus WKY. The secondary pressor response was attenuated in SHR compared to WKY in both the threshold dose (3.0 versus 0.1 microgram/kg i.v.) and maximum effect at high doses (52 versus 91% at 3.0 micrograms/kg i.v.). In conscious SHR and WKY, endothelin elicited comparable initial depressor responses with increases in heart rate; the secondary pressor responses were attenuated compared to those in anesthetized rats. Therefore endothelin elicits a prominent depressor response, which may be associated with afterload reduction, in SHR.
