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Am J Physiol Regul Integr Comp Physiol 279: R1701-R1706, 2000;
0363-6119/00 $5.00
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Vol. 279, Issue 5, R1701-R1706, November 2000

Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates

Glenn A. Reinhart, Lee C. Preusser, Terry J. Opgenorth, Craig D. Wegner, and Bryan F. Cox

Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois 60064-6119

This study was designed to quantify the long-term contribution of endogenous endothelin-1 (ET-1) and ETA receptors to the regulation of arterial pressure under normal conditions in nonhuman primates. Therefore, mean arterial pressure (MAP) and heart rate were measured 24 h/day with the use of telemetry techniques in conscious cynomolgus monkeys under control conditions, during administration of an ETA selective receptor antagonist (ABT-627; 5 mg/kg, 2 times a day by mouth, 4 days), and a 6-day posttreatment period. Systemic ETA blockade reduced MAP (24 h) from 89 ± 3 to 82 ± 2 and 79 ± 2 mmHg on days 1 and 4, respectively. Subsequently, MAP remained suppressed for 3 days posttreatment. Heart rate increased from 111 ± 5 to 122 ± 4 and 128 ± 6 beats/min on days 1 and 4 of ABT-627, respectively, and remained above control for 3 days posttreatment. Plasma ET-1 concentration increased from 1.0 ± 0.3 to 1.9 ± 0.4 pg/ml in response to ABT-627 (day 4) but decreased to control values 4 days posttreatment. These data demonstrate a physiologically important role for endogenous ET-1 and ETA receptors in the long-term regulation of arterial pressure and plasma ET-1 levels in the conscious nonhuman primate.

endothelium-derived factors; endothelin-receptor blockade


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