The role of sulfur dioxide as an endogenous gaseous vasoactive factor in synergy with nitric oxide

Abstract

To explore the physiological role of endogenous gaseous sulfur dioxide (SO 2) on vascular contractility and its underlying cellular and molecular mechanisms, vasodilation experiment of isolated rat thoracic aortic rings by gaseous SO 2 was carried out and the signal transduction pathways involved in the vascular effects of SO 2 were investigated. In the present study, SO 2 gas and SO 2 gas-bubbled solution (SO 2 stock solution) were first used to relax vascular tissues. The results show: (1) Gaseous SO 2 relaxed rat thoracic aortic rings in a dose-dependent manner (from 1 to 2000 μM). The vasorelaxant effect of SO 2 at physiological relevant and low concentrations (<450 μM) was endothelium-dependent, and at high concentrations (>500 μM) was endothelium-independent. (2) The vasorelaxation by addition of SO 2 stock solution (final concentrations ⩽2 mM) was actually caused by SO 2 molecules, not by sulfite or bisulfite, and the characteristic of vasorelaxation by SO 2 was different from that of sulfite and bisulfite. (3) The vasorelaxant effect of SO 2 was not due to the altered neurotransmitter release from the autonomous or nonadrenergic and noncholinergic (NANC) nerve endings, also not due to superoxide and hydrogen peroxide produced in the vascular tissues, also disapproving the involvement of prostaglandin, PKC, β-adrenoceptor and cAMP pathways. (4) The vasorelaxant effect of SO 2 at the physiological relevant and low concentrations was mediated by the cGMP pathway. (5) There was the synergistic effect on smooth muscle relaxation between much lower concentrations of SO 2 (3 μM) and NO (3 or 5 nM). These findings led to the conclusions: endogenous gaseous SO 2 was a vasoactive factor, which might regulate vascular smooth muscle tone in synergy with NO.