Reduced glutathione modulates the arachidonic acid induced coronary reactions

Abstract

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5-0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.

Vascular effects of arachidonic acid in the rat perfused heart: role of the endothelium, cyclooxygenase, cytochrome P450, and K+ channels

“…However, when tone was elevated with either nitroarginine or endothelin, we observed a predominant vasoconstrictor effect that was sometimes preceded or followed by a vasodilator effect. Under these conditions, our results were similar to those reported by Belo and Talesnik (16) and Talesnik and Tsoporis (18). Thus, the results of this study provide some insight into the apparently discrepant results reported by Shaffer and Malik (17) and Belo and Talesnik (16) and suggest that the level of tone dictates the formation or activity of vasoconstrictor/vasoconstrictor prostanoids.…”

“…Although cyclooxygenase-and cytochrome P450dependent vasorelaxant actions of AA have been described for canine and bovine coronary arteries, the actions of AA in the rat heart, which also reflects responses of the microvasculature, have not been fully characterized. Studies from almost two decades ago, before the importance of cytochrome P450 and K ϩ channels to vascular mechanisms was appreciated, addressed only the cyclooxygenase pathway in the vasoconstrictor/vasodilator effect of AA (15)(16)(17)(18) without any definition of the contribution of the endothelium, nitric oxide (NO), cytochrome P450, or K ϩ channels to the vasodilator component that is resistant to inhibition of cyclooxygenase (17). Moreover, in those studies, conflicting results were obtained which may reflect different experimental conditions.…”

Comparision of uroprotective activity of reduced glutathione with Mesna in Ifosfamide induced hemorrhagic cystitis in rats

“…This can be postulated by a marked development and enhancement of the vasodilator action of arachidonic acid modulated by GSH. [25]…”