Role of endogenous reactive oxygen derived species and cyclooxygenase mediators in 5-hydroxytryptamine-induced contractions in rat aorta: relationship to nitric oxide

Author： Srivastava P. Rajanikanth M. Raghavan S.A.V. Dikshit M.

Publisher： Academic Press

ISSN： 1043-6618

Source： Pharmacological Research, Vol.45, Iss.5, 2002-05, pp. : 375-382

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Abstract

Endogenous reactive oxygen species (superoxide anion, hydroxyl radical and hydrogen peroxide), endothelium-derived nitric oxide and cyclooxygenase mediators are involved in the regulation of vascular smooth muscle tone. An imbalance of these mediators can have profound implications in various cardiovascular disorders. Involvement of endogenous reactive oxygen species, endothelium-derived nitric oxide (NO) and cyclooxygenase mediators in 5-hydroxytryptamine- (5-HT-) induced contractions of endothelium intact rat aortic rings have been investigated in the present study. The contribution of each of the endogenous reactive oxygen species in mediating 5-HT-induced contractions was studied by pretreating the rings with their respective scavengers. Pretreatment of the rings with superoxide dismutase (superoxide radical scavenger), catalase (H ₂O ₂inactivator), mannitol (extracellular OH ·scavenger), or thiourea (intracellular OH · radical scavenger) significantly depressed the 5-HT-induced contractions in the aortic rings. The responses to 5-HT in the presence of SOD or catalase were augmented byl -NAME pretreatment. Though aminotriazole partially inhibited the catalase activity, it inhibited 5-HT-induced contractions significantly. The results obtained thus suggest that endogenous generation of ROS (O₂·^-, H ₂O ₂and OH ·) modulates 5-HT-induced rat aortic ring contractions. In addition, H ₂O ₂generated in the endothelium seems to regulate the vascular response and also act as a mediator to release other vasoactive substances. Basal production of NO by the endothelium seems to affect the vascular response due to its interaction with ROS mediators.