Prominent depressor response to endothelin in spontaneously hypertensive rats.
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.
Winquist
R J
RJ
Department of Pharmacology, Merck, Sharp & Dohme Research Laboratories, West Point, PA 19486.
Bunting
P B
PB
Garsky
V M
VM
Lumma
P K
PK
Schofield
T L
TL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016232:Endothelins; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016232:Endothelins; D010455:Peptides