The Role Of Hydrogen Sulfide In Regulating Carotid Sinus Baroreceptor Reflex In Renovascular Hypertensive Rats

Hydrogen sulfide (H₂S) is a colorless, toxic gas with smell of rotten eggs. It has been recognized as the third new gaseous signal molecule following nitric oxide (NO) and carbon monoxide (CO), and plays an important role in various systems. Hypertension is a common cardiovascular disease that may have serious impact on human health. Long-term hypertension can significantly increase the incidence of myocardial infarction, stroke or chronic renal failure, etc. Additionally, the influence of H₂S on hypertension has drawn more and more attention. It is well known that baroreflex plays an important role in maintaining blood pressure and our group has provided lots of evidence that H₂S dose-dependently facilitated carotid baroreflex in physiological conditions, by the means of opening KATP channels and further closing calcium channels. Renovascular hypertension is caused by renovascular disease with reduced renal blood flow and renal ischemia, and finally will lead to hypertension. Some evidiences have showed dysfunction of the baroreflex in hypertension. Baroreceptors are known to reset to operate in a higher pressure range in hypertensive rats. In the study, the aim is to observe the effects of H₂S on carotid sinus carotid baroreflex and the underlying mechanism in renovascular hypertensive rats.1 Chronical exogenous administration of sodium hydrosulfide regulates carotid sinus baroreflex in renovascular hypertensive ratsObjective: To study the effects of exogenous chronically administration of sodium hydrosulfide (NaHS) on carotid sinus baroreflex (CSB) during the formation of renovascular hypertension. Methods: Seven-week-old male Sprague-Dawley rats were randomly divided into 4 groups (n=6): control group, sham group, two-kidney-one-clip group (2K1C group), 2K1C+NaHS group. In the 2K1C+NaHS group, the rats were injected intraperitoneally with NaHS (donor of H₂S, 56μmol/kg) daily from the first day after the 2K1C operation. The control group, sham group and 2K1C group were injected with the same dose of normal saline. After 4 weeks, by using the experimental procedure designed by our own laboratory, the functional curve of carotid sinus baroreflex and the changes of arterial blood pressure were recorded in male rats with perfused carotid sinus, the plasma concentration of H₂S and angiotensin II (Ang II) were studied as well.Results: (1) In the 2K1C group, compared with the control group and sham group, the functional curve of the baroreflex shifted to the right and upward, the peak slope (PS) and the reflex decrease (RD) decreased markedly. (2) Compared with 2K1C group, NaHS (56μmol/L) administration shifted the functional curve of the baroreflex to the left and downward, with a marked increase in PS and RD. PS increased from 0.31±0.02 to 0.37±0.03, RD increased from 34.50±1.87 mmHg to 38.67±1.86 mmHg; threshold pressure (TP) decreased from 76.34±1.60 mmHg to 72.16±2.46 mmHg; equilibrium pressure (EP) decreased from 137.32±1.17 mmHg to 117.33±2.63 mmHg; saturation pressure (SP) decreased from 195.95±0.76 mmHg to 192.76±1.42 mmHg. (3) The tail arterial pressure and the Ang II plasma concentration in 2K1C group were significantly higher than the control group and sham group, whereas the plasma level of H₂S was significantly decreased. Exogenous administered of NaHS markedly lowered rats tail arterial pressure and Ang II concentration, increased H₂S production.Conclusion: The sensitivity of carotid sinus baroreceptor reflex was decreased in renovascular hypertensive rats, chronical exogenous administration of NaHS facilitates carotid sinus baroreflex with decreased blood pressure. 2 Acute sodium hydrosulfide perfusion regulates carotid sinus baroreceptor reflex in renovascular hypertensive ratsObjective: To study the effects of acute perfusion of sodium hydrosulfide (NaHS) on carotid sinus baroreflex (CSB) in renovascular hypertensive rats.Methods: Seven-week-old male Sprague-Dawley rats were randomly divided into 6 groups: control group (n=6), sham group (n=6), two-kidney-one-clip hypertension group (2K1C group) (n=6), 2K1C+NaHS group (n=18), 2K1C+NaHS+Gli group (n=6), 2K1C+NaHS+Bay K 8644 group (n=6). After 4 weeks, the functional curve of carotid sinus baroreflex was measured by recording the changes of arterial pressure with perfused islolated carotid sinus using the experimental procedure designed by our laboratory.Results: (1) NaHS (25, 50 and 100μmol/L) facilitated CSB, which shifted the functional curve of the baroreflex to the left and downward, with a marked increase in peak slope (PS) and reflex decrease in blood pressure (RD) in a concentration-dependent manner. PS increased from 0.31±0.03 to 0.37±0.02, 0.43±0.03, 0.47±0.01 respectively. RD increased from 34.67±1.37 mmHg to 40.83±1.94, 45.33±1.75, 50.17±1.72 mmHg; threshold pressure (TP) decreased from 76.68±2.75 mmHg to 71.83±1.37, 64.96±2.65, 58.75±2.26 mmHg; equilibrium pressure (EP) decreased from 137.15±1.22mmHg to 134.14±2.08, 129.78±1.37, 125.59±2.05 mmHg; saturation pressure (SP) decreased from 195.78±2.11 mmHg to 192.93±1.48, 185.40±1.51, 179.20±1.38 mmHg respectively. (2) Pretreatment with glibenclamide (20μmol/L), a KATP channel blocker, and Bay K 8644 (an agonist of calcium channels, 500 nmol/L) eliminated the effect of H₂S on CSB.Conclusion: In renovascular hypertensive rats, acute administration of NaHS in perfusion exerts an important role in facilitating the isolated CSB by opening KATP channels and subsequent closing of the calcium channels.