Hydrogen Sulfide Improves The Response To Angiotensin Ⅱ In The Offspring Of Renovascular Hypertensive Rats

Objective: To determine whether exogenous administration of NaHS（a H₂S donor）during perinatal or postnatal stage can decrease the blood pressure,incidence of prehypertension,and the response to Angiotensin II in the offspring of renovascular hypertensive（RVH）rats.Methods:1 Preparation of animal model: Renovascular hypertensive rats were made by two-kidney one-clip（2K1C）.2 In this study,the following four groups of rats were used: offspring of Sprague-Dawley rats(F_SD);offspring of RVH rats(F_1NF_2N);offspring of hydrogen sulfide treated RVH rats which were raised without hydrogen sulfide(F_1HF_2N),the pregnant rats of this group were administrated intraperitoneally with NaHS（56 μmol/kg/day）in the whole perinatal stage;offspring of RVH rats which were raised with hydrogen sulfide(F_1NF_2H),the offspring rats of this group received NaHS 56umol/kg/day intraperitoneally from the fifth week after delivery.3 Every two weeks,systolic blood pressure（SBP）was measured by non-invasive tail-cuff plethysmograpy in all the offspring rats from the eighth week to the sixteenth week.4 The offspring rats were mounted on a stereotaxic apparatus and implanted with a lateral cerebroventricular cannula,then AngⅡwas injected to the lateral ventricle via the cannula connected to a microsyringe with a polyethylene tube.5 MAP,HR and RSNA were recorded simultaneously by Powerlab software（ADInstruments,Australia）.6 Western blot was used to observe the protein expression of AT₁ R,ATRAP and Nox2,p67^phox,NT.Results:1 Compared with F_SD group,the SBP and the incidences of prehypertension in male offspring of F_1NF_2N were significantly increased from the eighth week to the sixteenth week,and the above effects were significantly improved by exogenous administration of hydrogen sulfide in F_1HF_2N and F_1NF_2H group.2 The SBP of female offspring in F_1NF_2N group was significantly increased when compared with F_SD group from the eighth week to the sixteenth week but there was a significantly decrease both in F_1HF_2N group at the eighth week and F_1NF_2H group at the sixteenth week.The incidences of prehypertension had no significant differences in each group.3 Intracerebroventricular infusion of AngⅡ10ng increased the MAP,HR and RSNA in male offspring rats,and the increases in MAP and RSNA were higher in F_1NF_2N group than F_SD group（ΔMAP: 10.83±0.48 vs.8.17±0.70 mmHg;ΔRSNA: 25.90±2.53% vs.16.78±1.70%,P<0.05）.Compared with F_1NF_2N group,the above effects in F_1HF_2N and F_1NF_2H group were siginificantly attenuated（F1HF2N group,ΔMAP: 8.33±0.61 mmHg;ΔRSNA: 16.42±1.98%;F1NF2H group,ΔMAP: 8.17±0.60 mmHg;ΔRSNA: 16.68±2.41%,P<0.05）.The effects of intracerebroventricular injection of AngⅡ30ng had the same tendency with AngⅡ10ng and produced a greater response.The changes of HR had no significant differences in each group.4 Intracerebroventricular infusion of AngⅡ10ng incrased the MAP,HR,RSNA in female offspring,but there were no significant differences in each group.However,the AngⅡ30ng induced increases in MAP and RSNA were higher in F_1NF_2N group than F_SD group（ΔMAP: 10.83±0.60 vs.8.08±0.45 mmHg;ΔRSNA: 26.88±2.61% vs.19.59±1.50%,P<0.05）.Compared with F_1NF_2N group,the pressor effects in F_1HF_2N and F_1NF_2H group siginificantly decreased（F1HF2N group,ΔMAP: 7.67±0.84 mmHg;ΔRSNA: 19.78±1.50%;F1NF2H group,ΔMAP: 7.50±0.67 mmHg;ΔRSNA: 18.82±2.25%,P<0.05）.The changes of HR had no significant differences in each group.5 Western blot analysis showed that the protein expression of AT₁ R,Nox2,p67^phox and NT were significantly increased,whereas the protein expression of ATRAP was significantly decreased in NTS in the male offspring of F_1NF_2N group,exogenous administration of hydrogen sulfide during perinatal or postnatal stage significantly reversed the above changes.6 Compared with female offspring of F_SD group,AT₁ R protein expression in F_1NF_2N group was significantly increased,whereas the protein expression of ATRAP,Nox2,p67^phox and NT had no significant differences in each group,exogenous administration of hydrogen sulfide during perinatal or postnatal stage significantly decreased the protein expression of AT₁ R when compared with F_1NF_2N group.Conclusion:1 Exogenous administration of hydrogen sulfide during perinatal or postnatal stage can significantly improve the systolic blood pressure,incidence of prehypertension,and the response to Angiotensin II via inhibiting the AngⅡ-ATlR pathway and downregulating the oxidative stress-related protein expression.2 The influence of renovascular hypertensive on its offspring have gender differences,we speculate that the estrogen may play a protective role through inhibiting the oxidative stress-related protein expression.