We studied the effects of the H2S donor Na2S on the mean arterial blood pressure (MAP) and heart and breathing rates of anesthetized Wistar rats in the presence and absence of captopril. Bolus administration of Na2S (1-4 μmol/kg) into the right jugular vein transiently decreased heart and increased breathing rates; at 8-30 μmol/kg, Na2S had a biphasic effect, transiently decreasing and increasing MAP, while transiently decreasing heart rate and increasing and decreasing breathing rate. These results may indicate independent mechanisms by which H2S influences MAP and heart and breathing rates. The effect of Na2S in decreasing MAP was less pronounced in the presence of captopril (2 μmol/l), which may indicate that the renin-angiotensin system is partially involved in the Na2S effect. Captopril decreased H2S-induced NO release from S-nitrosoglutathione, which may be related to some biological activities of H2S. These results contribute to the understanding of the effects of H2S on the cardiovascular system., M. Drobná, A. Misak, T. Holland, F. Kristek, M. Grman, L. Tomasova, A. Berenyiova, S. Cacanyiova, K. Ondrias., and Obsahuje bibliografii
Gasotransmitters represent a subfamily of the endogenous gaseous signaling molecules that include nitric oxide (NO), carbon monoxide
(CO), and hydrogen sulphide (H2S). These particular gases share many common features in their production and function, but they fulfill their physiological tasks in unique ways that differ from those of classical signaling molecules found in tissues and organs. These gasotransmitters may antagonize or potentiate each other’s cellular effects at the level of their production, their downstream molecular targets and their direct
interactions. All three gasotransmitters induce vasodilatation, inhibit apoptosis directly or by increasing the expression of anti-apoptotic genes, and activate antioxidants while inhibiting inflammatory actions. NO and CO may concomitantly participate in vasorelaxation, anti-inflammation and angiogenesis. NO and H2S collaborate in the regulation of vascular tone. Finally, H2S may upregulate the heme oxygenase/carbon monoxide
(HO/CO) pathway during hypoxic conditions. All three gasotransmitters are produced by specific enzymes in different cell types that include cardiomyocytes, endothelial cells and smooth muscle cells. As translational research on gasotransmitters has exploded over the past years, drugs that alter the production/levels of the gasotransmitters themselves or
modulate their signaling pathways are now being developed. This review is focused on the cardiovascular effects of NO, CO, and H2S. Moreover, their donors as drug targeting the cardiovascular system are briefly described.
The aim of the present study was to explore whether hydrogen sulfide (H2S) protects against ischemic heart failure (HF) by inhibiting the necroptosis pathway. Mice were randomized into Sham, myocardial infarction (MI), MI + propargylglycine (PAG) and MI + sodium hydrosulfide (NaHS) group, respectively. The MI model was induced by ligating the left anterior descending coronary artery. PAG was intraperitoneally administered at a dose of 50 mg/kg/day for 4 weeks, and NaHS at a dose of 4mg/kg/day for the same period. At 4 weeks after MI, the following were observed: A significant decrease in the cardiac function, as evidenced by a decline in ejection fraction (EF) and fractional shortening (FS), an increase in plasma myocardial injury markers, such as creatine kinase-MB (CK-MB) and cardiac troponin I (cTNI), an increase in myocardial collagen content in the heart tissues, and a decrease of H2S level in plasma and heart tissues. Furthermore, the expression levels of necroptosis-related markers such as receptor interacting protein kinase 1 (RIP1), RIP3 and mixed lineage kinase domain-like protein (MLKL) were upregulated after MI. NaHS treatment increased H2S levels in plasma and heart tissues, preserving the cardiac function by increasing EF and FS, decreasing plasma CK-MB and cTNI and reducing collagen content. Additionally, NaHS treatment significantly downregulated the RIP1/RIP3/MLKL pathway. While, PAG treatment aggravated cardiac function by activated the RIP1/RIP3/MLKL pathway. Overall, the present study concluded that H2S protected against ischemic HF by inhibiting RIP1/RIP3/MLKL-mediated necroptosis which could be a potential target treatment for ischemic HF.
The purpose of the present study was to define the indirect central effect of hydrogen sulfide (H2S) on baroreflex control of sympathetic outflow. Perfusing the isolated carotid sinus with sodium hydrosulfide (NaHS), a H2S donor, the effect of H2S was measured by recording changes of renal sympathetic nerve activity (RSNA) in anesthetized male rats. Perfusion of isolated carotid sinus with NaHS (25, 50, 100 μmol/l) dose and timedependently inhibited sympathetic outflow. Preconditioning of glibenclamide (20 μmol/l), a ATP-sensitive K+ channels (KATP) blocker, the above effect of NaHS was removed. With 1, 4-dihydro-2, 6-dimethyl-5-nitro-4-(2-[trifluoromethyl] phenyl) pyridine-3-carboxylic acid methyl ester (Bay K8644, 500 nmol/l) pretreatment, which is an agonist of L-calcium channels, the effect of NaHS was eliminated. Perfusion of cystathionine γ-lyase (CSE) inhibitor, DL-propargylglycine (PPG, 200 μmol/l), increased sympathetic outflow. The results show that exogenous H2S in the carotid sinus inhibits sympathetic outflow. The effect of H2S is attributed to opening KATP channels and closing the L-calcium channels., Qi Guo, Yuming Wu, Hongmei Xue, Lin Xiao, Shneg Jin, Ru Wang., and Obsahuje bibliografii
Hydrogen sulfide (H2S), an endogenous “gasotransmitter”, exists in the central nervous system. However, the central cardiovascular effects of endogenous H2S are not fully determined. The present study was designed to investigate the central cardiovascular effects and its possible mechanism in anesthetized rats. Intracerebrovent ricular (icv) injection of NaHS (0.17~17 μ g) produced a significant and dose-dependent decrease in blood pressure (BP) and heart rate (HR) (P<0.05) compared to control. The higher dose of NaHS (17 μ g, n=6) decreased BP and HR quickly of rats and 2 of them died of respiratory paralyse. Icv injection of the cystathionine beta-synthetase (CBS) activator s-adenosyl-L-methionine (SAM, 26 μ g) also produced a significant hypotension and bradycardia, which were similar to the results of icv injection of NaHS. Furthermore, the hypotension and bradycardia induced by icv NaHS were effectively attenuated by pretreatment with the KATP channel blocker glibenclamide but not with the CBS inhibitor hydroxylamine. The present study suggests that icv injection of NaHS produces hypotension and bradycardia, which is dependent on the KATP channel activation., W.-Q. Liu ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy