新型气体信号分子硫化氢在高血压发病中的变化及意义

目的研究自发性高血压大鼠(SHR)胸主动脉硫化氢(H2S)转化率及血浆H2S水平的变化,探讨H2S在自发性高血压形成中的作用.方法 4周龄雄性SHR大鼠24只,随机分为SHR对照组(n=8)、SHR+硫氢化钠(NaHS)组(n=8)及SHR+DL-propargylglycine(PPG,胱硫醚γ-裂解酶抑制剂)组(n=8).同样周龄相同遗传背景的正常Wistar大鼠(Wistar-Kyoto rats, WKY) 24只,随机分为WKY对照组(n=8)、WKY+外源性H2S供体硫氢化钠(NaHS)组(n=8)及WKY+PPG组(n=8).SHR对照组及WKY对照组大鼠每日腹腔注射无菌注射用水2.5 ml,SHR+NaHS组及WKY+NaHS组每日腹腔注射NaHS (剂量为56 μmol/kg),SHR+PPG组及WKY+PPG组大鼠分别每日腹腔注射PPG(剂量为37.5 mg/kg).5周后检测各组大鼠血压、左心室与全心重量比值、胸主动脉H2S转化率与血浆H2S水平.结果实验5周后,各组SHR大鼠胸主动脉H2S转化率及血浆H2S水平均明显低于相应WKY大鼠(P＜0.05),SHR+PPG组胸主动脉H2S转化率及血浆H2S水平与SHR对照组相近,SHR+NaHS组的胸主动脉H2S转化率及血浆H2S水平均明显高于SHR对照组( P＜0.05);WKY+PPG组的胸主动脉H2S转化率及血浆H2S水平均显著低于WKY对照组(均P＜0.05),WKY+NaHS组的胸主动脉H2S转化率显著高于WKY对照组(P＜0.05),其血浆H2S水平与WKY对照组相近;各组SHR大鼠血压较相应WKY大鼠显著升高(均P＜0.05),SHR+PPG组大鼠血压与SHR对照组相似,SHR+NaHS组血压较SHR对照组明显降低(P＜0.05);WKY+PPG组血压较WKY对照组显著升高(P＜0.05),WKY+NaHS组血压与WKY对照组相比差异无显著性.结论内源性H2S生成减少是维持机体基础血压的重要因素,也是自发性高血压形成的重要原因,给予外源性H2S提供了干预大鼠高血压形成的新思路.

Changes of endogenous hydrogen sulfide (H2S) in hypertensive rats

OBJECTIVE: Hydrogen sulfide, a well known toxic gas, has been found to play important roles in many organs and tissues, especially in cardiovascular system recently. The aim of this study was to explore the producing rate of hydrogen sulfide (H(2)S) in aorta and the level of H(2)S in plasma of spontaneous hypertensive rats (SHR), and to study the role of H(2)S on the development of hypertension. METHODS: Twenty-four male SHR rats at the age of 4 weeks were randomly divided into SHR control group, SHR + NaHS (H(2)S donor) group and SHR + DL-propargylglycine (PPG) group, respectively. Another twenty-four male WKY rats were also divided into WKY control group, WKY + NaHS group and WKY + PPG group. SHR control and WKY control rats were injected with water. Rats of SHR + NaHS group and WKY + NaHS group were injected with NaHS, and rats of SHR + PPG group and WKY + PPG group were injected with PPG every day. Five weeks later, the blood pressure and the left-to-whole heart weight ratio were determined. The producing rate of H(2)S in aorta and the H(2)S level in plasma were also detected. RESULTS: The producing rate of H(2)S in aorta and the plasma level of H(2)S in SHR groups were all less than those of the corresponding WKY groups, however, the differences between SHR + PPG group and WKY + PPG group were not significant (P > 0.05). The producing rate of H(2)S and the plasma level of H(2)S in SHR + PPG group were similar to those of SHR control group. The producing rate of H(2)S and the plasma level of H(2)S in SHR + NaHS group were higher than those of SHR control. Both the producing rate and the plasma level of H(2)S in WKY + PPG group were less than those of WKY control. The producing rate of H(2)S in aorta of WKY + NaHS group was higher than that of WKY controls, while the plasma level of H(2)S in WKY + NaHS group was not different from that of WKY controls significantly. The blood pressure of SHR groups increased compared with that of WKY groups (P < 0.05). The blood pressure of SHR + PPG group was similar to that of SHR controls, while the blood pressure of SHR + NaHS reduced significantly compared with that of SHR controls. The blood pressure of WKY + PPG group was higher than that of WKY controls while the blood pressure of WKY + NaHS was similar to that of WKY controsl. CONCLUSIONS: H(2)S plays an important role in maintaining normal pressure and the reduced production of endogenous H(2)S is an essential factor in the development of spontaneous hypertension. Exogenous H(2)S provides a new way for interfering with the progression of hypertension.