RESUMO
Oxidative stress is associated with many cardiovascular diseases, such as hypertension and arteriosclerosis. Oxidative stress reportedly activates the L-type voltage-gated calcium channel (VDCCL) and elevates [Ca2+]i in many cells. However, how oxidative stress activates VDCCL under clinical setting and the consequence for arteries are unclear. Here, we examined the hypothesis that hydrogen peroxide (H2O2) regulates membrane potential (Em) by altering Na+ influx through cation channels, which consequently activates VDCCL to induce vasoconstriction in rat mesenteric arteries. To measure the tone of the endothelium-denuded arteries, a conventional isometric organ chamber was used. Membrane currents and Em were recorded by the patch-clamp technique. [Ca2+]i and [Na+]i were measured with microfluorometry using Fura2-AM and SBFI-AM, respectively. We found that H2O2 (10 and 100 µM) increased arterial contraction, and nifedipine blocked the effects of H2O2 on isometric contraction. H2O2 increased [Ca2+]i as well as [Na+]i, and depolarised Em. Gd3+ (1 µM) blocked all these H2O2-induced effects including Em depolarisation and increases in [Ca2+]i and [Na+]i. Although both nifedipine (30 nM) and low Na+ bath solution completely prevented the H2O2-induced increase in [Na+], they only partly inhibited the H2O2-induced effects on [Ca2+]i and Em. Taken together, the results suggested that H2O2 constricts rat arteries by causing Em depolarisation and VDCCL activation through activating Gd3+-and nifedipine-sensitive, Na+-permeable channels as well as Gd3+-sensitive Ca2+-permeable cation channels. We suggest that unidentified Na+-permeable cation channels as well as Ca2+-permeable cation channels may function as important mediators for oxidative stress-induced vascular dysfunction.