Hemodynamic effects of a selective endothelin--a receptor antagonist in deoxycorticosterone acetate-salt hypertensive rats.
The time-course changes in blood pressure (BP), cardiac output (CO), and total peripheral conductance (TPC) were investigated during a bolus i.v. infusion of BMS-182874, a selective ETA receptor antagonist, in conscious, unrestrained DOCA-salt hypertensive rats and Sham-operated control rats (SHAM). BP was recorded with radiotelemetry devices and CO with ultrasonic transit-time flow probes. In contrast to vehicle-treated controls, BMS-182874 reduced BP and increased TPC in DOCA-salt hypertensive rats but not in SHAM-rats. A small increase in CO tended to oppose the BP-lowering effect of the antagonist. The results suggest that the role of ETA 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 CO.
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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; D002302:Cardiac Output / Q000187:drug effects; D003619:Dansyl Compounds / Q000494:pharmacology*; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D003619:Dansyl Compounds; D065128:Endothelin Receptor Antagonists; D044022:Receptor, Endothelin A; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide; D003900:Desoxycorticosterone