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

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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.

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