Ethacrynic Acid

Abstract

We examined the hemodynamic effect of ethacrynic acid (EA), a diuretic, and sulfhydryl binding reagent in the dog to determine whether EA attenuated the response to nitroglycerin (GTN) in vivo or in vitro in rings of dorsal pedal artery (DPA). Six dogs (group A) received infusions of GTN (21 μg/min i.v.) before and after EA (0.75 mg/kg). EA produced a marked diuresis [289 ml ± 41 (SD) urine during 60 min]; 10 min after EA and before substantial diuresis, there was a transient increase in heart rate (HR) from 117 beats/min ± 29 to 143 beats/min ± 28 and in mean arterial pressure (MAP) from 137 mm Hg ± 18 to 144 mm Hg ± 17 (p < 0.005). Intravenous GTN resulted in a similar decline in systolic blood pressure before (14.7% ± 6.4) and after (9.4% ±8.1) EA. We also studied two additional groups of dogs that received either EA (0.75 mg/kg) or saline, and urine output was replaced with saline. Similar results were obtained as with group A. In the in vitro studies, 75 rings of DPA from 14 dogs were pretreated with EA at low (1.6 × 10⁻⁵M), medium (8.3 × 10⁻⁵M), or high (1.7 × 10⁻⁴M) doses or EA solvent (control) for 30 min, and dose-response curves were performed for GTN (10⁻⁹ to 10⁻⁵M). In control rings, the maximum relaxation achieved with GTN was 89% ± 5.8 inhibition of phenylephrine-induced tone; with both the medium and high EA doses, the response to GTN was partially attenuated. These data show that EA produces a small and transient increase in HR and MAP before diuresis, that EA (0.75 mg/kg) does not affect the in vivo response to i.v. GTN, indicating that a clinical EA-GTN interaction is unlikely; and that the sulfhydryl reagent EA partially attenuates the in vitro response to GTN.