Quanxi Zhang

The vasorelaxant effect and its mechanisms of sodium bisulfite as a sulfur dioxide donor

To study the biological role of bisulfite on vascular contractility and its underlying cellular and molecular mechanisms, to explore whether bisulfite can be used as a sulfur dioxide (SO(2)) donor in the biological experiments, the vasorelaxant effects of sodium bisulfite and sodium sulfite on isolated rat thoracic aortic rings were compared; and the signal transduction pathways and the ion channels involved in the vascular effects of bisulfite were investigated. The results show that: (1) Sodium bisulfite relaxed rat thoracic aortic rings in a concentration-dependent manner (from 100 to 4000 μM); however, sodium sulfite at 500 and 1000 μM caused vasoconstriction, and only at higher concentrations (from 2000 to 4000 μM) it caused vasorelaxation in a concentration-dependent manner. (2) The vasorelaxation caused by the bisulfite at low concentrations (≤500 μM) was endothelium-dependent, but at high concentrations (≥1000 μM) it was endothelium-independent. (3) The vasorelaxation by the bisulfite at the low concentrations was partially mediated by the cGMP pathway and the vasorelaxation was related to big-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, but not due to prostaglandin, protein kinase C (PKC) and cAMP pathways. (4) The vasorelaxation by the bisulfite at high concentrations was partially inhibited by tetraethylammonium (TEA) and glibenclamide, suggesting that the vasorelaxation was related to ATP-sensitive K(+) channel (K(ATP)) and L-type calcium-channel. These results led to the conclusion that bisulfite (HSO(3)(-)) might be a vasoactive factor and sodium bisulfite can be used as a SO(2) donor for the study of SO(2) biology.

Vasodilator effect of gaseous sulfur dioxide and regulation of its level by Ach in rat vascular tissues

To explore the toxicological and physiological role of gaseous SO2 on vascular contractility and its level in vascular tissues, a vasodilation study of isolated rat thoracic aortic rings by gaseous SO2 was carried out. The level of SO2 in vascular tissue was assayed using a modified high-performance liquid chromatographic method with fluorescence detection (HPLC-FD). The results show that gaseous SO2 (from 1 μM to 2000 μM) relaxed rat thoracic aortic rings in a dose-dependent manner. The physiological concentrations of SO2 in thoracic aortic tissues and plasma in rats were 127.76 ± 31.34 μM and 16.77±8.24 μM, respectively; The vasorelaxant effect of gaseous SO2 at physiological and low concentrations (<450 μM) was endothelium dependent, and at high concentrations (>500 μM) was endothelium independent. The results also show that SO2 could be endogenously generated in vascular tissues, and mainly in vascular endothelial cells; acetylcholine (Ach) increased the SO2 level in vascular tissue, and noradrenaline (NE) decreased the SO2 level. These findings demonstrate that gaseous SO2 is a vasorelaxant substance, and the vasorelaxant effect of gaseous SO2 is much stronger than that of its derivatives sulfite and bisulfite, which result from the inactivation process of SO2 gas transmitter by which SO2 is hydrated to form sulfite, and the latter is enzymatically oxidized to form sulfate. These findings also demonstrate that endogenous SO2 level in vascular tissue may be regulated by Ach and NE.

Effects of gaseous sulfur dioxide and its derivatives on the expression of KATP, BKCa and L-Ca2+ channels in rat aortas in vitro

Epidemiological investigations have revealed that sulfur dioxide (SO2) exposure is linked to cardiovascular diseases. Our previous study indicated that the vasorelaxant effect of SO2 might be partly related to ATP-sensitive K(+) (KATP), big-conductance Ca(2+)-activated K(+) (BKCa) and L-type calcium (L-Ca(2+)) channels. The present study was designed to further investigate the effects of gaseous SO2 and its derivatives on the gene and protein expression of these channels in the rat aortas in vitro. The results showed that the mRNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2 and SUR2B of the rat aortas in SO2 and its derivatives groups were higher than those in control group. Similarly, the expression of the BKCa channel subunits α and β1 was increased by SO2 and its derivatives. However, SO2 and its derivatives at 1500μM significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. Histological examination of the rat aorta tissues showed moderate injury of tunica media induced by SO2 and its derivatives at 1500μM. These results suggest that SO2 and its derivatives can activate the KATP and BKCa channels by increasing the expression of Kir6.1, Kir6.2, SUR2B and α, β1, respectively, while also inhibiting the L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of the rat aortas. The molecular mechanism of the vasorelaxant effect of SO2 and its derivatives might be related to the expression changes of KATP, BKCa and L-Ca(2+) channel subunits, which may play a role in the pathogenesis of SO2-associated cardiovascular diseases.

The molecular mechanism of the effect of sulfur dioxide inhalation on the potassium and calcium ion channels in rat aortas.

This study investigated the molecular mechanism of the effect of sulfur dioxide (SO2) on the expression of adenosine triphosphate (ATP)-sensitive potassium ion (K+; KATP) channel, big-conductance calcium ion (Ca2+)-activated K+ (BKCa) channel, and L-type (L-Ca2+) channel subunits in rat aortas with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot. The results showed that the messenger RNA and protein levels of the KATP channel subunits Kir6.1, Kir6.2, and sulfonylurea receptor 2B (SUR2B) of rat aortas were significantly increased by SO2 at 14 mg/m3, whereas the levels of SUR2A were not changed. SO2 at all the treated concentrations markedly raised the expression of the BKCa channel subunits α and β1. SO2 at 14 mg/m3 significantly decreased the expression of the L-Ca2+ channel Cav1.2 and Cav1.3. The histological examination of rat aorta tissues showed moderate injury of tunica media in the presence of SO2 at 14 mg/m3. These suggest that SO2 can activate the KATP and BKCa channels by upregulating the expression of Kir6.1, Kir6.2, SUR2B, BKCa α, and BKCa β1, while inhibit the L-Ca2+ channels by downregulating the expression of Cav1.2 and Cav1.3 in rat aortas. The molecular mechanism of SO2-induced vasorelaxant effect might be linked to the changes in expression of these channel subunits, which plays an important role in the pathogenesis of SO2-associated cardiovascular diseases.

Effects of sodium metabisulfite on the expression of BKCa, KATP, and L-Ca2+ channels in rat aortas in vivo and in vitro

Sodium metabisulfite (SMB) is most commonly used as the preservative in many food preparations and drugs. So far, few studies about its negative effects were reported. The purpose of this study was to investigate the effect of SMB on the expression of big-conductance Ca(2+)-activated K(+) (BKCa), ATP-sensitive K(+) (KATP), and L-type calcium (L-Ca(2+)) channels in rat aorta in vivo and in vitro. The results showed that the mRNA and protein levels of the BKCa channel subunits α and β1 of aorta in rats were increased by SMB in vivo and in vitro. Similarly, the expression of the KATP channel subunits Kir6.1, Kir6.2, and SUR2B were increased by SMB. However, SMB at the highest concentration significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. These results suggest that SMB can activate BKCa and KATP channels by increasing the expression of α, β1, and Kir6.1, Kir6.2, SUR2B respectively, while also inhibit L-Ca(2+) channels by decreasing the expression of Cav1.2 and Cav1.3 of aorta in rats. The molecular mechanism of SMB-induced vasorelaxant effect might be related to the expression changes of BKCa, KATP, and L-Ca(2+) channels subunits. Further work is needed to determine the relative contribution of each channel in SMB-mediated vasorelaxant effect.

The vasorelaxant mechanisms of methanol on isolated rat aortic rings: Involvement of ion channels and signal transduction pathways.

It is reported that methanol is generally used as an industrial solvent, antifreeze, windshield washer fluid, cooking fuel and perfume. Methanol ingestion can lead to severe metabolic disturbances, blindness, or even death. So far, few studies about its negative effects on cardiovascular system have been reported. The purpose of this study was to determine the vasoactive effect of methanol and roles of ion channels and signal transduction pathways on isolated rat aorta. The results suggested that the mechanism of methanol-induced vasorelaxation at low concentrations (<500 mM) was mediated by ATP-sensitive K+ (KATP) and L-type Ca2+ channels, but the mechanism at high concentrations (>600 mM) was related to KATP, voltage-dependent K+, big-conductance Ca2+-activated K+, L-type Ca2+ channels as well as prostacyclin, protein kinase C, β-adrenoceptors pathways. In addition, methanol induced a dose-dependent inhibition of vasoconstrictions caused by calcium chloride, potassium chloride, or norepinephrine. Further work is needed to investigate the relative contribution of each channel and pathway in methanol-induced vasoactive effect.

The molecular mechanisms of sodium metabisulfite on the expression of KATP and L-Ca2+ channels in rat hearts

Sodium metabisulfite (SMB) is used as an antioxidant and antimicrobial agent in a variety of drugs and foods. However, there are few reported studies about its side effects. This study is to investigate the SMB effects on the expression of ATP-sensitive K(+) (KATP) and L-type calcium (L-Ca(2+)) channels in rat hearts. The results show that the mRNA and protein levels of the KATP channel subunits Kir6.2 and SUR2A were increased by SMB; on the contrary, SMB at 520 mg/kg significantly decreased the expression of the L-Ca(2+) channel subunits Cav1.2 and Cav1.3. This suggests that SMB can activate the expression of KATP channel by increasing the mRNA and protein levels of Kir6.2 and SUR2A, while it inhibits the expression of L-Ca(2+) channels by decreasing the mRNA and protein levels of Cav1.2 and Cav1.3 in rat hearts. Therefore, the molecular mechanism of the SMB effect on rat hearts might be related to the increased expression of KATP channels and the decreased expression of L-Ca(2+) channels.