Hussain Afthab, Maddock Helen, Al-Rajaibi Hajar, Carson Ray J
Biomolecular Sciences, Faculty of Health & Life Sciences, Coventry University, Coventry, UK;
Sultan Qaboos Univ Med J. 2011 May;11(2):236-44. Epub 2011 May 15.
Hydrogen sulphide has been identified as a gas signalling molecule in the body, and has previously been shown to have vasorelaxant properties. The aim of the study was to investigate the effects of sodium hydrosulphide (NaHS), a hydrogen sulphide donor, on heart rate (HR), left ventricular developed pressure (LVDP) and coronary flow (CF) in the isolated perfused rat heart.
A Langendorff isolated heart preparation was used to investigate the effect of a dose range of sodium hydrosulphide, in the presence and absence of inhibitors, on heart rate, left ventricular developed pressure and coronary flow.
Sodium hydrosulphide caused a significant decrease in heart rate at a concentration of 10-3 M (P <0.001). This decrease was partially inhibited by glibenclamide, a K(ATP) channel blocker (P <0.05); L-NAME, a nitric oxide synthase inhibitor (P <0.001), and methylene blue (P <0.001), but not by H-89, a protein kinase A inhibitor. Sodium hydrosulphide significantly increased coronary flow at concentrations of 10-4 - 10-3M (P <0.05). This response was significantly increased in the presence of L-NAME (P <0.001) and methylene blue (P <0.001), whereas H-89 inhibited the increase in coronary flow due to sodium hydrosulphide (P <0.001). Sodium hydrosulphide significantly decreased LVDP at all concentrations (P <0.001). In the presence of glibenclamide and H-89, the time period of the decrease in LVDP due to sodium hydrosulphide was extended (P <0.001), whereas methylene blue and L-NAME caused a significant reduction in the response to sodium hydrosulphide (P <0.05, P <0.01 respectively).
Sodium hydrosulphide reduced heart rate and LVDP, and increased coronary flow in the isolated perfused rat heart; however, the mechanisms of action could not be fully elucidated.
硫化氢已被确认为体内的一种气体信号分子,此前已证明其具有血管舒张特性。本研究的目的是探讨硫化氢供体硫氢化钠(NaHS)对离体灌注大鼠心脏心率(HR)、左心室舒张末压(LVDP)和冠状动脉血流量(CF)的影响。
采用Langendorff离体心脏制备方法,研究不同剂量硫氢化钠在有无抑制剂存在的情况下对心率、左心室舒张末压和冠状动脉血流量的影响。
硫氢化钠在浓度为10-3 M时可显著降低心率(P <0.001)。这种降低被格列本脲(一种K(ATP)通道阻滞剂,P <0.05)、L-NAME(一种一氧化氮合酶抑制剂,P <0.001)和亚甲蓝(P <0.001)部分抑制,但未被蛋白激酶A抑制剂H-89抑制。硫氢化钠在浓度为10-4 - 10-3M时可显著增加冠状动脉血流量(P <0.05)。在L-NAME(P <0.001)和亚甲蓝(P <0.001)存在的情况下,这种反应显著增强,而H-89抑制了硫氢化钠引起的冠状动脉血流量增加(P <0.001)。硫氢化钠在所有浓度下均可显著降低LVDP(P <0.001)。在格列本脲和H-89存在的情况下,硫氢化钠引起的LVDP降低的时间延长(P <0.001),而亚甲蓝和L-NAME则显著降低了对硫氢化钠的反应(分别为P <0.05,P <0.01)。
硫氢化钠可降低离体灌注大鼠心脏的心率和LVDP,并增加冠状动脉血流量;然而,其作用机制尚不能完全阐明。