Comparative Effects of Ethacrynic Acid, Furosemide, and Diazoxide in the Perfused Dog Hindlimb

Abstract

The vasodilator effects of intravenous ethacrynic acid (EA), furosemide (F), and diazoxide (DZ) were compared in the hindlimb of anesthetized anephric dogs, perfused with a constant inflow of arterial blood. A dose-response relationship was demonstrated for all three agents. The curves for EA and F were parallel and relatively flat, with EA being 10 times more potent than F in producing vasodilatation of the perfused limb. The dose–response for DZ was steep and the maximal vasodilator response observed at the lowest dose of DZ (5 mg/kg) did not differ from that at the highest doses of EA (10 mg/kg) or F (100 mg/kg). The maximal vasodilator effect of DZ in the perfused hindlimb occurred within 2 min after intravenous administration. After the higher doses of F there was a transitory vasodilator effect within 2 min but the maximal and more persistent effect was not observed until much later. The mean time for maximal effect was 40 min for EA, 46 min for F, and 2 min for DZ. The time course of vasodilator effect and maximal observed effect for EA and F was not altered by intraarterial administration nor by sympathetic decentralization of the perfused hindlimb. We conclude that F, like EA, has a direct vasodilating effect on peripheral arterioles and both EA and F probably act by a different mechanism than DZ.