Effect of the dopamine beta-hydroxylase inhibitor, SK&F 102698, on blood pressure in the 1-kidney, 1-clip hypertensive dog.
The acute and chronic effects of a potent selective dopamine beta-hydroxylase inhibitor, SK&F 102698, were assessed in chronically instrumented 1-kidney, 1-clip Goldblatt hypertensive dogs. Blood pressure measured directly from either a carotid loop or from a vascular access port and cardiac output measured by impedence cardiography were monitored following acute (30 and 100 mg/kg, p.o.) and chronic (30 mg/kg/day for 4 days) administration of SK&F 102698. The data indicate that SK&F 102698 failed to alter blood pressure, cardiac output or total peripheral resistance after either acute or chronic administration. It is concluded that dopamine beta-hydroxylase inhibition with SK&F 102698 is not an effective antihypertensive agent in the 1-kidney, 1-clip Goldblatt hypertensive dog model.
Brooks
D P
DP
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa.
Fredrickson
T A
TA
Koster
P F
PF
Ruffolo
R R
RR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D004285:Dogs; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors*; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
C052414:1-(3,5-difluorobenzyl)imidazole-2-thiol; D007093:Imidazoles; D004299:Dopamine beta-Hydroxylase