Endogenously generated sulfur dioxide and its vasorelaxant effect in rats.

Aim: The present study was designed to explore the endogenous production and localization of the sulfur dioxide (SO₂)/aspartate aminotransferase pathway in vascular tissues of rats and to examine its vasorelaxant effect on isolated aortic rings, as well as the possible mechanisms. Methods: The content of SO₂ in the samples was determined by using high performance liquid chromatography with fluorescence detection. Aspartate aminotransferase activity and its gene expression were measured by an enzymatic method and quantitative RT–PCR, respectively. Aspartate aminotransferase mRNA location in aorta was detected by in situ hybridization. The vasorelaxant effect of SO₂ on isolated aortic rings of the rats was investigated in vitro. L-type calcium channel blocker, nicardipine, and L-type calcium channel agonist, Bay K8644, were used to explore the mechanisms by which SO₂ relaxed the aortic rings. Results: Aorta had the highest SO₂ content among the vascular tissues tested ( P<0.01). The aortic aspartate aminotransferase mRNA located in endothelia and vascular smooth muscle cells beneath the endothelial layer. Furthermore, a physiological dose of the SO₂ derivatives (Na₂SO₃/NaHSO₃) relaxed isolated artery rings slightly, whereas higher doses (1–12 mmol/L) relaxed rings in a concentration-dependent manner. Pretreatment with nicardipine eliminated the vasorelaxant response of the norepinephrine-contracted rings to SO₂ completely. Incubation with nicardipine or SO₂ derivatives successfully prevented vasoconstriction induced by Bay K8644. Conclusion: Endogenous SO₂ and its derivatives have a vasorelaxant function, the mechanisms of which might involve the inhibition of the L-type calcium channel. [ABSTRACT FROM AUTHOR]