Endothelin contributes to the hemodynamic effects of vasopressin in spontaneous hypertension.
Changes in blood pressure, cardiac output, and total peripheral conductance evoked by intravenous infusions of [Arg8]-vasopressin (vasopressin) were recorded before and after pretreatment with bosentan, a non-selective endothelin antagonist, in conscious unrestrained spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The presser effects of vasopressin were exaggerated in SHR compared to WKY. Pretreatment with bosentan failed to change hemodynamic responses of WKY to vasopressin, but it blunted the increases in blood pressure and the decreases in conductance evoked by vasopressin in SHR. In contrast, bosentan failed to change cardiac output responses of SHR to vasopressin. Except at the highest dose of vasopressin, bosentan abolished the exaggerated pressor responsiveness of the SHR to vasopressin. The results suggest that endothelin contributes to the exaggerated pressor responsiveness of SHR to vasopressin, and that this effect is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.
Balakrishnan
S M
SM
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Gopalakrishnan
V
V
McNeill
J R
JR
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D000077300:Bosentan; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013449:Sulfonamides / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D019332:Endothelin-1; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D014667:Vasopressins; D000077300:Bosentan