| Hydrogen sulfide (H2S) has recently been identified as a new gasotransmitter along side nitric oxide (NO) and carbon monoxide (CO) in the mammalian body. Endogenous H2S is formed from cysteine by pyridoxal-5′-phosphate (PLP)-dependent enzymes, including cystathionineβ-synthase (CBS) and cystathionineγ-lyase (CSE). PLP-independent enzyme, 3-mercaptopyruvate sulfurtransferase (3MST), is another possible candidate for H2S production. The expression of these enzymes is tissue-specific, while CBS and 3MST are highly expressed in brain, and CSE seems to be the mainly rate-limiting enzyme to catalyze the production of H2S in the cardiovascular system. H2S has been reported to exert important effects in mammalian tissues such as nervous system, cardiovascular system and gastrointestinal smooth muscle. The relaxation of H2S on smooth muscle is mediated by activating ATP-sensitive potassium (KATP) channels and also shows in synergy with nitric oxide. Exogenous administration of H2S in spontaneous hypertensive rats (SHRs) can suppress blood pressure, resulting in a decrease in vascular collagen accumulation. Additionally, H2S can dose-dependently facilitate the carotid sinus baroreflex, which indicate that H2S may regulate the hemodynamics also through its central effect on the baroreceptor reflex. The gaseous mediators, NO and H2S, play a number of important physiological and pathophysiological roles in the body. There is a research suggested that the plasma H2S concentration, vascular CSE activity and mRNA expression were obviously decreased, in NG-nitro-L-arginine methyl ester (L-NAME) induced hypertension rat model. H2S may be correlated with NO in some cardiovascular diseases. Therefore, H2S may have potential clinical value and the action of H2S is to be studied by further experiments. As we all known, the baroreflex is an important negative feedback system that stabilizes systemic arterial pressure (AP) during daily activities. Rostral ventrolateral medulla (RVLM) is a critical central region in the regulation of sympathetic outflow and plays an important role in the baroreflex. Nevertheless, the central effect of H2S on baroreflex control of sympathetic outflow and the direct effect of H2S on the cardiovascular center have not been reported, the goals of the present research were to observe these effects of H2S.1. Perfusion of Isolated Carotid Sinus with Hydrogen Sulfide Attenuated the Renal Sympathetic Nerve Activity in Anesthetized Male RatsAim: The present study was to define the effect of H2S on central region which regulates sympathetic outflow by perfusion of isolated carotid sinus with H2S.Methods: Sodium hydrosulfide (NaHS), a H2S donor, was perfused into isolated carotid sinus; the functional curve of the carotid sinus baroreflex was measured by recording changes in renal sympathetic nerve activity (RSNA) in anesthetized male rats.Results: (1) Perfusion of isolated carotid sinus with NaHS (25, 50, 100μmol/L) dose-dependently inhibited sympathetic outflow by enhancing the response of RSNA to the increased intrasinus pressure (ISP). RSNA was decreased to 84.95±3.58% (P<0.01), 63.89±2.53% (P<0.01) and 48.70±4.16% (P<0.01) compare with control. (2) Pretreatment with glibenclamide (20μmol/L), a KATP channels blocker, the above effect of NaHS was abolished. (3) Prior perfusion of Bay K8644 (500 nmol/L), an agonist of calcium channels, the effect of NaHS was eliminated. (4) Perfusion of CSE inhibitor, DL-propargylglycine (PPG, 200μmol/L), increased sympathetic outflow.Conclusion: The results suggest that perfusion of isolated carotid sinus with NaHS inhibits sympathetic outflow as evidenced by the decrease of RSNA. The effect is mediated by opening KATP channels and further closing the calcium channel in smooth muscle cells. Endogenous H2S maintain the blood pressure in a basal level through the tonically pathway to suppress the sympathetic vasomotor by activating the activity of the carotid sinus baroreflex (CSB).2. Microinjected Hydrogen Sulfide into Rostral Ventrolateral Medulla Decreases Sympathetic Outflow through an ATP-sensitive K+ Channels in Anesthetized Male RatsAim: The present study was to define the effect of H2S on central region which regulates sympathetic outflow by microinjection hydrogen sulfide into RVLM.Methods: NaHS was microinjected into RVLM, and blood pressure (BP), heart rate (HR) and RSNA were recorded simultaneously in anesthetized male rats.Results: (1) Microinjection of NaHS (4, 8, 16 mmol/L, 50 nl) into the RVLM decreased BP, HR and RSNA in a dose-dependent manner. Following microinjection of NaHS (4, 8, 16 mmol/L, 50 nl) into the RVLM, BP were significantly decreased from 107.05±3.72 mmHg to 95.39±3.03 mmHg (P<0.01), 101.80±3.83 mmHg to 82.90±9.59 mmHg (P<0.01) and 104.86±5.02 mmHg to 75.53±4.91 mmHg (P<0.01); HR was decreased from 416.50±14.98 bpm to 404.83±16.04 bpm (P<0.01), 398.83±25.10 bpm to 376.67±26.92 bpm (P<0.01) and 400.0±20.78 bpm to 368.83±19.38 bpm (P<0.01), and RSNA was decreased to 82.82±1.90% (P<0.01), 71.09±2.20% (P<0.01) and 54.42±5.23% (P<0.01), respectively. (2) Pretreatment with glibenclamide (40μmol/L, 50 nl), a KATP channels blocker, the above effects of NaHS were abolished. (3) Pretreatment with L-NAME (200μmol/L, 50 nl), an inhibitor of nitric oxide synthase (NOS), could partly abolish the effects of NaHS. (4) Prior microinjection of Bay K8644 (1μmol/L, 50 nl), an agonist of calcium channels, did not affect the effects of NaHS. (5) Infusion of the CBS inhibitor, hydroxylamine (HA, 30 mmol/L, 50 nl) increased BP, HR and RSNA.Conclusion: The results suggest that microinjection of NaHS into RVLM inhibits sympathetic outflow as evidenced by the decrease of BP, HR, and RSNA. The effect is mediated by opening KATP channels with partial involvement of NO. Endogenous H2S may tonically suppress the sympathetic vasomotor tone in vivo.
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