| Objective: Hydrogen sulfide (H2S) has long been recognized as a toxic gas in water and industrial air pollution. However, it was been recently found as a novel endogenous gasotransmitter generated in mammalian tissues. By analogy to other endogenous gaseous molecules, such as nitric oxide (NO), H2S is demonstrated to play important physiological and pathological roles in different systems including the central nervous system, immune system, and the cardiovascular system. In heart, H2S regulates the cardiac contractility and protects heart from ischemia injury. Studies reveal that endogenous H2S is involved in the regulation of blood pressure under baseline conditions. Meanwhile, NO, another endogenous gaso- transmitter, is also important to the regulation of cardiovascular activity. However, it is not yet clear whether H2S modulates cardiac function under hypertension or not. In addition, there is no information so far available about the cross-talk between NO and H2S in cardiac function of hypertensive rats. All of those prompted us to investigate the effects of H2S on cardiac function in hypertensive rats induced by Nω-nitro-L-arginine methyl ester (L-NAME), clarify the presence of cross-talk between NO and H2S and explore the potential mechanisms. Methods: Five groups of 4-week-old male normotensive Sprague-Dawley rats were investigated: control group, L-NAME group (L-NAME 50 mg/100 ml), L-NAME+NaHS (sodium hydrosulfide, a donor of H2S) group (L-NAME 50 mg/100 ml+NaHS 56μmol/kg/d), L-NAME+PPG (DL-propargylglycine) group (L-NAME 50 mg/100 ml+PPG 10 mg/kg/d), and L-NAME+PPG+NaHS group (L-NAME 50 mg/100 ml+NaHS 56μmol/kg/d+PPG 10 mg/kg/d). All rats except those in control group received L-NAME which was dissolved in the drinking water for 5 weeks, while the rats of control group received tap water for the same periods. NaHS and PPG were intraperitoneally injected with the same volume of 2.5 ml at the same time each day for 5 weeks, while rats in the control and L-NAME groups were injected with the same volume of sterile saline. The systolic blood pressure (SBP) was monitored with tail-cuff method each week. The rats were also weighed once a week, after the SBP measurements. Animals were sacrificed and studied after 5 weeks of treatment. In Langendorff isolated perfusion heart, cardiac function represented by coronary flow index (CFI), maximal positive and negative velocity of left ventricular pressure (±LVdP/dtmax) and left ventricular developing pressure (LVDP) was monitored for 15 min. In addition, some biochemical parameters including plasma concentration of NO and H2S, activity of nitric oxide synthases (NOS) and cystathionineγ-lyase (CSE) and expression of endothelial NOS (eNOS) and CSE protein in left ventricle (LV) tissue were evaluated.Results: (1) In L-NAME group, there was a notable increase of SBP, heart/body weight index (HWI) and left ventricular/body weight index (LVWI) as compared with control group, after 5 weeks of treatment. The cardiac function was significantly depressed, accompanied by the decrease in expression of eNOS protein, activity of NOS in LV tissue and plasma concentration of NO. Meanwhile, CSE activity and plasma H2S concentration were also lower than those of control group, but CSE protein expression in LV tissue was up-regulated significantly. (2) In L-NAME+NaHS group, treatment with NaHS could ameliorate cardiac dysfunction and abate the development of L-NAME-induced hypertension, as a result of the increase of plasma H2S level and LV tissue CSE activity. Meanwhile, eNOS protein expression in LV tissue was up-regulated and NOS activity was increased as compared with L-NAME group. (3) In L-NAME+PPG group, PPG (an inhibitor of CSE) had not aggravated cardiac dysfunction and development of hypertension and changed the plasma NO concentration and LV tissue NOS activity significantly, but LV tissue CSE activity and plasma H2S concentration were decreased and the expression of CSE protein was up-regulated as compared with L-NAME group. However, the cardiac dysfunction and the development of hypertension was exacerbated, accompanied by the decreases in eNOS protein expression, NOS and CSE activity in LV tissue and plasma NO and H2S concentration as compared with L-NAME+NaHS group. (4) In L-NAME+PPG+NaHS group, NaHS could inhibit the development of hypertension and increase±LVdP/dtmax as compared with L-NAME+PPG group.Conclusion: H2S may attenuate the L-NAME-induced hypertension and play a protective role in cardiac function of L-NAME-induced hypertensive rats. NO/NOS and H2S/CSE pathways may exert a synergistic cardioprotection against L-NAME-induced hypertension.
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