Total peripheral conductance mediates antihypertensive effect of nonpeptide mixed endothelin receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats.
The relative contribution of cardiac output (CO) and total peripheral conductance (TPC) to the changes in blood pressure (BP) evoked by an intravenous injection of bosentan, a nonpeptide mixed endothelin (ET) antagonist, were investigated in conscious unrestrained deoxycorticosterone acetate (DOCA)-salt hypertensive rats and sham-control rats. Blood pressure was recorded by radiotelemetry devices and CO by ultrasonic transit-time flow probes. Bosentan significantly reduced BP (from 141 +/- 3 to 111 +/- 3 mm Hg) and increased TPC (from 1.19 +/-0.1 to 1.72 +/- 0.2 mL/min/kg/mm Hg) in DOCA-salt hypertensive rats, but not in sham rats. An increase in CO opposed the BP-lowering effect of the antagonist. The results demonstrate that the role of ET receptors in the maintenance of the hypertensive state in the DOCA-salt model of hypertension is exerted at the level of the resistance vessels and not on factors that regulate cardiac output.
Yu
M
M
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; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D007262:Infusions, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D014655:Vascular Resistance / Q000502:physiology*
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D003900:Desoxycorticosterone; D000077300:Bosentan