Hydrogen Sulfide Facilitates Carotid Sinus Baroreceptor Activity In Renovascular Hypertensive Rats

Hydrogen sulfide（H₂S）has long been considered as a toxic gas with astrong characteristic rotten egg smell for hundreds years. There is clearevidence that H₂S is biosynthesized in mammalian tissues, and it has recentlybeen identified as the third new gaseous mediator along with nitric oxide （NO）and carbon monoxide （CO）. Endogenous H₂S exerts many importantphysiological and pathophysiological functions, including vasorelaxation,inhibition of smooth muscle cell proliferation, and antioxidatve actions. H₂Splays an important role in the regulation of cardiovascular diseases, such ashypoxic pulmonary artery hypertension, coronary heart disease andhypertension. Hypertension is a common cardiovascular system disease thatmay cause serious impact on human health. Long-term hypertension is a riskfactor for stroke, heart failure and end-stage renal disease, and ultimately leadsto death. So the prevention and treatment of hypertension is increasinglybecoming a hot spot in the study of medicine. Additionally, the influence ofH₂S on hypertension has drawn more and more attention. Renovascularhypertension, a frequently secondary hypertension, is renal artery stenosisdisease that causes renin change with reduced renal blood flow and renalischemia and eventually leads to high blood pressure. It is well known thatbaroreflex plays a crucial role in maintaining blood pressure. Some evidenceshave showed dysfunction of the baroreflex in hypertension. The effects of H₂Son carotid sinus baroreceptor activity have not been reported yet inrenovascular hypertensive rats. In our study, the aim is to observe the effectsof H₂S on carotid sinus carotid baroreceptor activity and the underlyingmechanism in renovascular hypertensive rats. Part I Chronical exogenous administration of sodiumhydrosulfide facilitates carotid sinus baroreceptor activityin renovascular hypertensive ratsObjective: To study the effects of exogenous chronically administrationof sodium hydrosulfide （NaHS） on carotid sinus baroreceptor activity （CBA）in the development of renovascular hypertension.Methods: Seven-week-old male Sprague-Dawley rats were randomlydivided into4groups （n=6）: sham group, sham+NaHS group，two-kidney-one-clip group （2K1C group） and2K1C+NaHS group. In thesham+NaHS group and2K1C+NaHS group, the rats were injectedintraperitoneally with NaHS （an H2S donor,56μmol/kg） daily from thesecond week after the2K1C operation. The sham group and2K1C group wereinjected with the same dose of normal saline. After4weeks, by using theexperimental procedure designed by our own laboratory, the functional curveof carotid baroreceptor （FCCB） was constructed and the functional parametersof carotid baroreceptor were measured by recording sinus nerve afferentdischarge in renovascular hypertensive rats with perfused isolated carotidsinus.Results:（1） In the2K1C group, compared with the sham group and sham+NaHS group, the FCCB shifted to the right and downward, the peak slope（PS） and peak integral value （PIV） decreased markedly.（2） Compared with2K1C group, NaHS （56μmol/L） administration shifted the FCCB to the rightand upward, with a marked increase in PS and RD. PS increased from3.46±0.17%mmHg-1to3.37±0.12（P<0.01）; threshold pressure （TP）decreased from77.02±0.76mmHg to74.17±0.64mmHg; saturation pressure（SP） decreased from213.20±2.08mmHg to206.00±3.89mmHg.（3） The tailarterial pressure in2K1C group was significantly higher than sham group andsham+NaHS group four weeks after surgery, whereas the plasma level of H2Swas significantly decreased. Exogenous administered of NaHS markedlylowered tail arterial pressure of the2K1C group and increased H2S production.Conclusion: The sensitivity of carotid sinus baroreceptor activity wasdecreased in renovascular hypertensive rats, chronical exogenousadministration of NaHS facilitated carotid sinus baroreceptor activity withdecreased blood pressure. Part II Acute sodium hydrosulfide perfusion facilitates carotid sinusbaroreceptor activity in renovascular hypertensive ratsObjective: To study the effects of acute perfusion of sodium hydrosulfide（NaHS） on carotid baroreceptor activity （CBA） in renovascular hypertensiverats.Methods: Seven-week-old male Sprague-Dawley rats were randomlydivided into5groups: sham group （n=6）, two-kidney-one-clip group （2K1Cgroup）（n=6）,2K1C+NaHS group （n=18）,2K1C+NaHS+Gli group （n=6）,2K1C+NaHS+Bay K8644group （n=6）. After5weeks, the FCCB wasmeasured by recording the changes of arterial pressure with perfused islolatedcarotid sinus using the experimental procedure designed by our laboratory.Results:（1） H2S （derived from NaHS）25,50and100μmol/L facilitatedcarotid sinus baroreceptor activity in renovascular hypertensive rats, whichshifted FCCB to the left and upward, with a marked increase in peak slope （PS）and peak integral value （PIV） in a concentration-dependent manner. PSincreased from3.46±0.17%mmHg-1to3.37±0.12,3.67±0.08,3.93±0.06%mmHg-1respectively. PIV increased from306.48±5.49%to337.45±5.12，350.75±4.95，365.55±5.36%respectivelyï¼› Threshold pressure （TP）decreased from77.02±0.76mmHg to71.66±1.39，69.82±1.04，67.47±0.82mmHgï¼›Saturation pressure （SP） decreased from213.20±2.08mmHg to204.82±2.91，194.61±1.73，186.73±1.80mmHg respectively.（2） Pretreatment with glibenclamide （20μmol/L）, a KATPchannel blocker, the above effects ofH₂S on carotid sinus baroreceptor activity were abolished.（3） Pretreatmentwith Bay K8644（an agonist of calcium channels,500nmol/L） eliminated therole of H₂S on carotid sinus baroreceptor activity.Conclusion: These data suggest that exogenous H₂S exerts a facilitatoryrole on isolated carotid sinus baroreceptor activity in renovascularhypertensive rats via opening KATPchannels and further closing the calciumchannels in vascular smooth muscle. Endogenous H₂S may activate theactivity of the carotid sinus baroreceptor activity in vivo.