Superoxide production in the isolated rabbit aorta and the effect of alloxan, indomethacin and nitrovasodilators

KF Heim, G Thomas and PW Ramwell

Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia.

The purpose of this investigation was to develop a simple model to assess superoxide production from isolated vessels and to use this model to study the effects of various compounds on superoxide generation. The established method of cytochrome C reduction by superoxide was modified to measure superoxide production in vascular rings from rabbit aortae. The diabetogenic compound alloxan significantly increased superoxide production in a concentration- dependent manner. The nitrovasodilators nitroprusside and minoxidil exhibited contrasting effects. Nitroprusside inhibited alloxan- stimulated production of superoxide, but minoxidil had no effect, suggesting different mechanisms of action for these drugs. The cyclooxygenase inhibitor indomethacin had no effect on the production of superoxide stimulated by alloxan, demonstrating that superoxide production induced by this compound is not affected by mechanisms involving cyclooxygenase. These data demonstrate the use of a simple, rapid and inexpensive method for measuring superoxide produced by intact vessels. This may be useful in testing drugs exhibiting antioxidant and vasoactive properties. Finally, because superoxide is implicated in the destruction of endothelium-derived relaxing factor, and the presence of the vasodilator nitroprusside reduces superoxide production, it is concluded that some nitrovasodilators may have additional vascular effects through the suppression of superoxide formation.

Volume 256, Issue 2, pp. 537-541, 02/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics

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