Hydroxyl radical: A possible mediator of nitroglycerin-induced vascular relaxation

Abstract

The endothelium-derived relaxing factor, nitric oxide (NO·), is involved in acetylcholine (Ach) and nitroglycerin (NTG)-induced relaxation of vascular smooth muscle. It is known that NO· interacts with the superoxide anion (O2·−) at physiological pH and this interaction leads to the generation of hydroxyl radicals (·OH). Hydroxyl radicals are known to induce dilation and act as mediators in acetylcholine (Ach)-induced relaxation of rabbit aortic smooth muscle. Thus, it was hypothesized that ·OH may be involved in NTG-induced relaxation. To test this hypothesis we investigated the effect of NTG on norepinephrine (NE)-precontracted isolated rabbit aortic rings in the absence and/or presence of O2·− [superoxide dismutase (SOD)] and ·OH scavengers [dimethylthiourea (DMTU) or mannitol]. Superoxide dismutase, DMTU, and mannitol markedly reduced NTG-induced relaxation of isolated rabbit aortic rings. Superoxide dismutase produced a 32% reduction in NTG-induced vasodilation. Pretreatment with DMTU and/or mannitol reduced NTG-induced relaxation by 56% and 49%, respectively. These results suggest that ·OH may be a mediator involved in NTG-induced vascular relaxation of rabbit aorta.