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Introduction
For hundreds of years, hydrogen sulfide
(H2S) has been known solely as a toxic gas with the smell of rotten eggs. Indeed,
H2S is gradually considered to be a broad spectrum toxicant; its major toxic effects are the toxicity of the central nervous
system (CNS) and the inhibition of the respiratory
system[1,2]. Recent studies have shown that
H2S is not only a chemical hazard in certain industrial manufacturing, but it can also be produced endogenously in mammalian tissues from
L-cysteine mainly by 3 enzymes: cystathionine
β-synthetase (CBS), cystathionine γ-lyase (CSE), and
3-mercapto-sulfurtransferase[3_6]. The expressions of CBS and CSE have been detected in various tissues.
H2S research has been recently focused on its
physiological effects and significance under disease conditions. Like nitric oxide (NO) and carbon monoxide (CO), which are
considered 2 gaseous transmitters, H2S has been shown to be the third gaseous transmitter and plays important roles, both
in normal physiology conditions and in the process/progress of several diseases.
H2S is a small molecule and can permeate membranes freely. The endogenous
H2S level is 0_46
µmol/L[7] in rat serum and 50_160 µmol/L in the
brain[4]. One-third of H2S remains undissociated in an aqueous solution and its solubility in lipophilic
solvents is 5-fold greater than in
water[8]. H2S is mostly metabolized to sulfate and thiosulfate via the oxidation metabolism
in mitochondria, and glutathione triggers the reaction. Very little of
H2S can be converted into lower toxic compounds of
methylmercaptan and dimethyl sulfate via the methylation
metabolism in cytosol. The metabolic product can exhaust
from the kidney and intestinal tract and lungs within 24 h, so
the endogenously-generated H2S under physiological
condition is hardly accumulated or toxic to cells due to the
balanced cellular metabolism of the
gas[9].
Although there are several excellent reviews on the
pathophysiological effects of H2S, such as those by
Wang[8] in 2002, Tang et
al[6] and Du et
al[10] in 2006, the present study will summarize the latest progress on
H2S studies concerning the CNS, cardiovascular system, a possible novel
mechanism for its motor effect, as well as the role of
H2S in ischemia.
Role of H2S in the CNS
Endogenous H2S is generated mainly by CBS in the
brain[11]. The transcriptional expression of CBS, but not CSE, in the
rat brain (hippocampus, cerebellum, cerebral, and brainstem)
was confirmed using the Northern blot assay; a similar
conclusion was confirmed in CBS knockout mice. The
production of H2S by CBS in the brain is regulated by
Ca2+ and calmodulin[12]. It is greatly enhanced by
the activation of glutamate receptors and electrical stimulation which could
cause influx of Ca2+. There are 2 mechanisms through which
CBS could produce H2S. First, CBS could catalyze the
production of H2S from cysteine by a β-elimination or a
α,β-elimination reaction; second, CBS can efficiently catalyze
the formation of H2S via the condensation of homocysteine
with cysteine, and the latter is not affected by
Ca2+ and calmodulin[13]. The regulation of CBS activity can affect brain
H2S formation. Eto et al found that sodium nitroprusside
(SNP), well known as a NO donor, could enhance CBS
activity by modifying 4 of 13 cysteine residues of CBS, but this
effect is independent of NO
production[14]. A human CBS complete genomic sequence has been
determined[15] and the transcriptional start sites of 5 CBS mRNA isoforms,
designated CBS-1a_1e, have been
mapped[16]. The 5 CBS transcripts begin with a different exon. CBS gene transcription
might be regulated by more than 1 promoter. Isoforms -1a
and -1b form the vast majority of transcripts. Regulation on
the transcriptional level is likely to be the mechanism of the
tissue-specific manner of CBS expression, and in some
senses, the expression of CBS in the brain could be
modulated at the gene level under physiological and
pathophysiological conditions.
The endogenous H2S by CBS in the brain indicates it has
physiological functions in the CNS.
N-methyl-D-aspartate (NMDA) receptors may be one of its targets. The activation
of NMDA receptors is required for the induction of
hippocampal long-term potentiation
(LTP)[17], a synaptic model of learning and memory. Because of the relatively high
concentration of endogenous H2S in the brain (50_160 µmol/L),
the physiological concentration of H2S facilitates the
induction of LTP by enhancing NMDA receptor-induced
currents[11]. This activation could be blocked by an adenylyl
cyclase-specific inhibitor, indicating that the modulation of NMDA
receptors by H2S is induced by the enhancement of cAMP
production[18]. This function ranked
H2S as a neuromodulator in the brain. Another study showed that
H2S could increase intracellular
Ca2+ and induce Ca2+ waves in neighboring
astrocytes[19]. Therefore,
H2S may mediate signals between neurons and glia and regulate synaptic activity by
modulating the activity of both neurons and glia.
In addition to its role in signal transduction,
H2S can protect neuron cells from oxidative stress, not only by
increasing the levels of antioxidant
glutathione[20], but also by activating the
K+ATP and Cl_
channels[21]. In human cultured neuron cells,
H2S could inhibit peroxynitrite
(ONOO_), which is an important mediator of human neurodegenerative disease,
inducing tyrosine nitration, a1-antiproteinase inactivation,
cell toxicity, intracellular protein oxidation, and protein
nitration. This antioxidant action of
H2S suggests it functions as an endogenous
ONOO_ scavenger[22]. Oxidative
stress is responsible for neuronal damage and degenerates
in brain disorders. These observations suggest that
H2S may act as a neuroprotectant against oxidative stress.
The concentration of H2S in the brain changes with CNS
diseases. The levels of H2S decreased by 55% in the brains
of Alzheimer's disease (AD) patients and CBS activity was
also dramatically decreased[23], but the level of AdoMet, a
CBS activator, is low in AD brains. The CBS activity was
reduced in another disease,
homocystinuria[24]. Febrile seizure (FS) frequently occurs in children. Both
gamma-aminobutyric acid (GABA) B receptor
(GABABR) subunits and the H2S/CBS system were involved in FS.
H2S functioned as a protective factor in the development of FS
through regulating
GABABR[25]. Intriguingly, the levels of
CBS in Down's syndrome brains were approximately 3 times
greater than those in normal
individuals[26]. The role of
H2S in CNS diseases is not clear and needs to be explored in
future. The progress of this field can provide novel therapy
in clinical trials.
Role of H2S in the cardiovascular system
Hosoki et al found that H2S could be generated in the
homogenates of the portal vein and thoracic
aorta[4]. They also identified that CSE was the major enzyme to generate
H2S in these tissues by detecting the transcription of the
mRNA of CSE with the Northern blot assay. The expression
levels of CSE mRNA varied in different types of vascular
tissues and was ranked as artery>aorta>tail
artery>mesenteric artery[27]. A recent study has shown that in the heart,
there is very few CBS, but plentiful
CSE[28]. It seems that CBS does not play a major role in the cardiovascular system
under physiological conditions. These observations
suggested the potential physiological functions of
H2S/the CSE system in the cardiovascular system. The biosynthetic
underlying mechanism of action of H2S is summarized in
Figure 1[3].
H2S can be produced enzymatically in vascular tissues
and relaxes vascular smooth muscles both in vivo
and in vitro[4,29]. This vasorelaxant effect is most probably caused
by opening vascular smooth muscle cells (VSMC)
KATP channels which leads to membrane
hyperpolarization[27]. Therefore,
H2S may reduce extracellular
Ca2+ entry and relax vascular tissues. The vasorelaxation induced by
H2S can be attenuated by the removal of the endothelium, since
H2S may facilitate the release of vasorelaxant factors from the
endothelium, including NO and the endothelium-derived
relaxing factor. As opposed to NO and CO,
H2S-induced vasorelaxation is not mediated by the cGMP signaling
pathway. This indicates that H2S is a novel endogenous
gaseous modulator of vascular contractility. At the same
time, similar to NO and CO, H2S could inhibit VSMC
proliferation and induce apoptosis in
vitro[30,31]. Using cultured VSMC, exogenous
H2S could dose-dependently suppress the proliferation of VSMC through the mitogen-activated
protein kinase (MAPK) signaling pathway. Studies using
molecular means to overexpress CSE in cultured VSMC found
that endogenous H2S could also attenuate the rate of cell
proliferation and increase the rate of cell apoptosis. The
effect is via the activation of MAPK and caspase-3. The
possible signaling pathway is shown in Figure 2. So
H2S is not only a vasorelaxant, but also an important regulator of
cell growth and may thereby attenuate the structural
remodeling of vessel tissues. This can help us understand the
mechanism of some vascular diseases and provide links to
new therapeutic methods.
The pathophysiological role of H2S in some
cardiovascular diseases has been explored. The endogenous
H2S/CSE pathway participated in the pathophysiological process
in vascular diseases, such as spontaneous
hypertension[32], hypoxia-induced pulmonary hypertension
(HPH)[33_35], and high pulmonary blood flow-induced pulmonary
hypertension[36,37]. Hypertension is one of the most common
cardiovascular diseases and its mechanism is not fully understood
yet. Vasoconstriction and structural remodeling by VSMC
proliferation are essential processes in hypertension
develop-ment. In the spontaneous hypertension rat model, the plasma
level of H2S is low and the activity of CSE is suppressed.
The exogenous administration of H2S not only attenuated
the elevation of blood pressure and vessel remodeling, but
also recovered the H2S level and CSE
activity[32]. Guang et al's study found that there was dysfunction of the
H2S/CSE system in L-NAME-induced hypertension rats and that
exogenous H2S could effectively prevent the development
of hypertension[38]. The exogenous
H2S-induced positive feedback on CSE activity is different from its negative
feedback in physiological
conditions[39]. A recent study reported
that the exogenous administration of H2S downregulated
osteopontin gene expression and ameliorated vascular
calcification (which is a common finding in many diseases, such
as hypertension, atherosclerosis, diabetes, chronic renal
failure, aging, and arterial
stenosis)[40]. As it is known, the baroreflex is the major method of blood pressure modulation.
Exogenous H2S could facilitate carotid sinus baroreflex (CSB)
by opening KATP channels and further closing the calcium
channels in vascular smooth muscle which suggests that
endogenous H2S might activate the activity of the CSB
in vivo[41]. In HPH pathophysiological processes, the similar
dysfunction of H2S/CSE was found, and exogenous
H2S could inhibit the proliferative cell nuclear antigen (PCNA)
and U-II expressions in the pulmonary wall to depress the
proliferation of pulmonary artery smooth muscle cells and
reduce the expression of collagen I and III, elastin, and
TGFβ3 to decrease the hypoxic pulmonary vascular structural
remodeling[34,35]. Olson et al's recent study on the
mechanical and electrical responses of select blood vessels to
hypoxia and H2S suggested that
H2S served as an O2 sensor/transducer in the vascular responses to hypoxia. The
inhibition of H2S synthesis inhibited the hypoxic response of
vertebrate blood vessels and the concentration of
H2S in the vessel was regulated by the balance between endogenous
H2S production and its oxidation by available
O2[42]. The exogenous supply of
H2S could alleviate the elevation of pulmonary arterial pressure. At the same time, exogenous
supply of propargylglycine (PPG, inhibitor of CSE), plasma
CO level, and the expressions of the HO-1 protein and mRNA
in pulmonary arteries decreased. The results showed that
H2S could play a regulatory role in the pathogenesis of HPH
through the upregulation of the CO/HO
pathway[43]. How-ever, in aortic smooth muscle cells, Jin
et al's study proved that endogenous CO/HO and the
H2S/CSE pathways downregulated each other under physiological
conditions[44]. Exogenous
H2S also ameliorated pulmonary vascular
structural remodeling induced by high pulmonary blood flow,
downregulated PCNA expression and the ERK/MAPK signal pathway, inhibited the NO/NO synthase pathway, and
enhanced the CO/HO pathway in rats with high pulmonary
blood flow[36,37]. These studies suggested that endogenous
H2S was one of the key factors in hypertension development
and that the deficit of the H2S/CSE system was one of the
major causes of hypertension.
Some studies have proven that the concentration of
arterial endogenous H2S was significantly increased in both
septic and endotoxic shock rats, which suggested that
endogenous H2S was still involved in physiological and
pathophysiological processes during
shock[45].
Human cystathioninuria, which is characterized by high
plasma homocysteine and cystathionine, is concerned with
a wide range of disease associations, such as
cardiovascular injury. Its genomic basis has been shown to be 2
nonsense mutations and 2 sense mutations in
CSE[46].
It has been reported that H2S also activates the
KATP channel in mitochondria and sarcolemmal
KATP channels in cardiac myocytes and has potent cardioprotective
effects[47_49]. The cardioprotection of
H2S was also demonstrated in rat isolated ventricular
myocytes[50]. NaHS could concentration-dependently increase the cell viability and the
percentage of rod-shaped cells, which were exposed to severe
metabolic inhibition solution. NaHS-induced cardioprotection
following metabolic inhibition preconditioning could be
blocked by PPG and HMR-1098 (a sarcolemmal
KATP blocker). Pretreatment with
L-NAME to block endogenous NO production could also attenuate the cardioprotective effect of
NaHS. These results indicate that H2S may protect the heart
most probably by activating sarcolemmal
KATP, which is different from its vasorelaxant effect. NO also plays an
important role in cardioprotection. Further, the cardioprotective
effect has similar characteristics to the time-course of
ischemic preconditioning; it suggests the possible
protective role of H2S in ischemic myocardium. This has been
proven by a recent study[51]. In a rat model of myocardial
infarction (MI), NaHS treatment could decrease the
mortality rate of MI rats and diminish infarct size as shown in
Figure 3. The vessel dilating/relaxing effects of NaHS may
dilate coronary arteries and increase coronary blood flow in
ischemic diseases, thus reducing cellular damage from
ischemia. This heart protective effect could be abolished by
the administration of PPG. The results were further
confirmed by our in vitro hypoxic model (Figure 4). It has been
suggested that endogenous H2S might provide a novel
approach to the treatment of MI. Further work needs to be
performed to explore whether or not the mechanism of this
effect concerns the KATP channel.
H2S also showed a cardio-protective effect in another isoproterenol injection-induced
myocardial ischemic injury model in which the plasma
H2S concentration and CSE activity decreased. The
administration of NaHS could effectively protect myocytes and
contractile activity[52].
Excitatory motor effect of H2S
In contrast to the vasorelaxant effect, NaHS produced
concentration-dependent contractile responses in the
detrusor muscle of the rat urinary
bladder[53]. This response exhibited rapid and persistent tachyphylaxis similar to the
responses of capsaicin[54,55]. The response was abolished
by high-capsaicin pretreatment which could desensitize
capsaicin-sensitive primary afferent neurons or the pretreatment
of tissues with a combination of tachykinin natural killer
(NK)1 and NK2 receptor-selective antagonists. At the same time,
the response to NaHS is mostly resistant to tetrodotoxin, as
is the effect of capsaicin in this
organ[56]. These results show pharmacological evidence that
H2S stimulates capsaicin-sensitive primary afferent nerve terminals with the
consequent release of tachykinins, which in turn produces
contractile responses of the detrusor muscle. In further studies,
the same researchers demonstrated that the transient
receptor potential vanilloid receptor 1 (TRPV1, also called the
capsaicin receptor) selective antagonist capsazepine and
SB366791 could not affect the H2S contractile
activity[53]. However, the unselective cation channel blocker, ruthenium
red, almost abolished the contraction similar to its effect on
capsaicin, which provided 2 hypotheses: first,
H2S stimulates the TRPV1 receptor by a different way from those known
activators; second, H2S might stimulate other receptors
present on the terminals of capsaicin-sensitive sensory
neurons.
TRPV1 was cloned from rat sensory
neurons[57] in 1997. TRPV1 is non-selective cation channel with high
permeability of Ca2+ and could be activated by chemical and physical
stimuli, such as capsaicin, low pH[58], noxious heat,
ananda-mide[59], 12-hydroperoxyeicosatetraenoic
acid[60], and
N-arachidonoyl-dopamine[61]. The influx of
Na+ causes primary sensory neuron depolarization and the initiation of
action potentials. In particular, the influx of
Ca2+ resulted in the local release of neuropeptides, including the calcitonin
gene-related peptide and the tachykinins, substance P, and
neurokinin A. TRPV1-positive neurons are not only afferent
neurons which are involved in the perception of somatic and
visceral pain, but also have a sensory effector function. These
neuropeptides act on different effector cells and cause
different responses, including neurogenic inflammation,
thermal hyperalgesia, airway constriction, and
vasodilatation[62]. TRPV1 is highly expressed in primary sensory neurons of
the trigeminal, vagal, and dorsal root ganglion with C- and
A-δ fibers, which are called nociceptive neuron. Studies also
show that TRPV1 is expressed in non-neuronal cells,
including epithelial cells of the
urothelium[63],
keratinocytes[64], and skeletal
muscles[65]. These features of TRPV1 indicate its
broad physiological and pathophysiological functions.
In addition to the detrusor muscle, NaHS increases
sensory neuropeptide release in the guinea pig airways and
causes in vivo bronchoconstriction and microvascular
leakage in a capsazepine-sensitive
manner[66]. This novel mechanism may contribute to the irritant action of
H2S in the respiratory system, possibly through TRPV1 activation. Further
research is still required in order to prove whether or not
H2S acts as a endogenous ligand of TRPV1. It will be interesting
to detect the odorous activator of TRPV1 and its
undergoing mechanism. Therefore, previous studies on the
physiological and pathophysiological roles of
H2S need re-evaluation based on this mechanism.
Concluding remarks
H2S has been shown to be an important biological
molecule in the last 2 decades. In addition to its neuromodulator
and cardiovascular protection effects, studies also show that
H2S has various effects in mammalian tissues, such as the
relaxation effect of the ileum, which indicates that
endogenous H2S could regulate alimentary contractile
functions[67]. H2S has been described as an endogenous mediator with
diverse biological effects in a study, including playing an
important role in endotoxin-induced
inflammation[68]. The studies of the physiological functions of
H2S and its underlying mechanism, the regulation of
H2S concentration and activity, and/or the expression of CBS and/or CSE and its
interaction with some diseases may have a significant
impact in our understanding of the pathogenesis of these
diseases, as well as having far-reaching clinical and
therapeutic implications. Further research needs to be
undertaken to find new therapeutic methods and ruling out
possible side-effects.
References
1 Beauchamp RJ, Bus JS, Popp JA, Boreiko CJ, Andjelkovich DA.
A critical review of the literature on hydrogen sulfide toxicity.
Crit Rev Toxicol 1984; 13: 25_97.
2 Guidotti TL. Hydrogen sulphide. Occup Med (Lond) 1996; 46:
367_71.
3 Moore PK, Bhatia M, Moochhala S. Hydrogen sulfide: from the
smell of the past to the mediator of the future? Trends Pharmacol
Sci 2003; 24: 609_11.
4 Hosoki R, Matsuki N, Kimura H. The possible role of hydrogen
sulfide as an endogenous smooth muscle relaxant in synergy with
nitric oxide. Biochem Biophys Res Commun 1997; 237:
527_31.
5 Kimura H, Nagai Y, Umemura K, Kimura Y. Physiological roles
of hydrogen sulfide: synaptic modulation, neuroprotection, and
smooth muscle relaxation. Antioxid Redox Signal 2005; 7:
795_803.
6 Tang CS, Li XH, Du JB. Hydrogen sulfide as a new endogenous
gaseous transmitter in the cardiovascular system. Curr Vasc
Pharmacol 2006; 4: 17_22.
7 Zhao W, Ndisang JF, Wang R. Modulation of endogenous
production of H2S in rat tissues. Can J Physiol Pharmacol 2003; 81:
848_53.
8 Wang R. Two's company, three's a crowd: can
H2S be the third endogenous gaseous transmitter? FASEB J 2002; 16:
1792_8.
9 Furne J, Springfield J, Koenig T, DeMaster E, Levitt MD.
Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat
tissues: a specialized function of the colonic mucosa. Biochem
Pharmacol 2001; 62: 255_9.
10 Du JB, Zhang CY, Yan H, Tang CS. A newly found gasotransmitter,
hydrogen sulfide, in the pathogenesis of hypertension and other
cardiovascular diseases. Curr Hypertens Rev 2006; 2:
123_6.
11 Abe K, Kimura H. The possible role of hydrogen sulfide as an
endogenous neuromodulator. J Neurosci 1996; 16:
1066_71.
12 Eto K, Kimura H. The production of hydrogen sulfide is
regulated by testosterone and
S-adenosyl-L-methionine in mouse brain.
J Neurochem 2002; 83: 80_6.
13 Chen X, Jhee KH, Kruger WD. Production of the neuromodulator
H2S by cystathionine beta-synthase via the condensation of
cysteine and homocysteine. J Biol Chem 2004; 279:
52082_6.
14 Eto K, Kimura H. A novel enhancing mechanism for hydrogen
sulfide-producing activity of cystathionine beta-synthase. J Biol
Chem 2002; 277: 42680_5.
15 Avila MA, Berasain C, Torres L, Martin-Duce A, Corrales FJ,
Yang H, et al. Reduced mRNA abundance of the main enzymes
involved in methionine metabolism in human liver cirrhosis and
hepatocellular carcinoma. J Hepatol 2000; 33: 907_14.
16 Bao L, Vlcek C, Paces V, Kraus JP. Identification and tissue
distribution of human cystathionine beta-synthase mRNA
isoforms. Arch Biochem Biophys 1998; 350: 95_103.
17 Harris EW, Ganong AH, Cotman CW. Long-term potentiation
in the hippocampus involves activation of
N-methyl-D-aspartate receptors. Brain Res 1984; 323:
132_7.
18 Kimura H. Hydrogen sulfide induces cyclic AMP and modulates
the NMDA receptor. Biochem Biophys Res Commun 2000;
267: 129_33.
19 Nagai Y, Tsugane M, Oka J, Kimura H. Hydrogen sulfide induces
calcium waves in astrocytes. FASEB J 2004; 18:
557_9.
20 Kimura Y, Kimura H. Hydrogen sulfide protects neurons from
oxidative stress. FASEB J 2004; 18: 1165_7.
21 Kimura Y, Dargusch R, Schubert D, Kimura H. Hydrogen sulfide
protects HT22 neuronal cells from oxidative stress. Antioxid
Redox Signal 2006; 8: 661_70.
22 Whiteman M, Cheung NS, Zhu YZ., Chu SH, Siau JL, Wong
BS, et al. Hydrogen sulphide: a novel inhibitor of hypochlorous
acid-mediated oxidative damage in the brain? Biochem Biophys Res
Commun 2005; 326: 794_8.
23 Eto K, Asada T, Arima K, Makifuchi T, Kimura H. Brain
hydrogen sulfide is severely decreased in Alzheimer's disease. Biochem
Biophys Res Commun 2002; 293: 148_58.
24 Hu FL, Gu Z, Kozich V, Kraus JP, Ramesh V, Shih VE. Molecular
basis of cystathionine beta-synthase deficiency in pyridoxine
responsive and nonresponsive homocystinuria. Hum Mol Genet
1993; 2: 1857_60.
25 Han Y, Qin J, Bu DF, Chang XZ, Yang ZX, Du JB.
Gamma-aminobutyric acid B receptor regulates the expression of
hydrogen sulfide/cystathionine-beta-synthase system in recurrent
febrile seizures. Zhongguo Dang Dai Er Ke Za Zhi 2006; 8:
141_3 Chinese.
26 Ichinohe A, Kanaumi T, Takashima S, Enokido Y, Nagai Y,
Kimura H. Cystathionine beta-synthase is enriched in the brains
of Down's patients. Biochem Biophys Res Commun 2005; 338:
1547_50.
27 Zhao W, Zhang J, Lu Y, Wang R. The vasorelaxant effect of
H2S as a novel endogenous gaseous K(ATP) channel opener. EMBO
J 2001; 20: 6008_16.
28 Geng B, Yan H, Zhong GZ, Zhang CY, Chen XB, Jiang HF,
et al. Hydrogen sulfide: a novel cardiovascular functional regulatory
gas factor. Beijing Da Xue Xue Bao 2004; 36: 106. Chinese.
29 Zhao W, Wang R. H(2)S-induced vasorelaxation and underlying
cellular and molecular mechanisms. Am J Physiol Heart Circ
Physiol 2002; 283: 474_80.
30 Du JB, Yan H, Cheung YF, Geng B, Jiang HF, Chen XB,
et al. The possible role of hydrogen sulfide as a smooth musle cell
proliferation inhibitor in rat cultured cells. Heart Vessels 2004; 19:
75_80.
31 Yang G, Sun X, Wang R. Hydrogen sulfide-induced apoptosis of
human aorta smooth muscle cells via the activation of
mitogen-activated protein kinases and caspase-3. FASEB J 2004; 18:
1782_4.
32 Yan H, Du JB, Tang CS. The possible role of hydrogen sulfide on
the pathogenesis of spontaneous hypertension in rats. Biochem
Biophys Res Commun 2004; 313: 22_7.
33 Zhang C, Du J, Bu DB, Yan H, Tang X, Si
Q, et al. The regulatory effect of endogenous hydrogen sulfide on hypoxic pulmonary
hypertension. Beijing Da Xue Xue Bao 2003; 35: 488_93.
Chinese.
34 Li XH, Du JB, Shi L, Li J, Tang XY, Qi
JG, et al. Down-regulation of endogenous hydrogen sulfide pathway in pulmonary
hypertension and pulmonary vascular structural remodeling induced
by high pulmonary blood flow in rats. Circ J 2005; 69: 1418_24.
35 Jin HF, Cong BL, Zhao B, Zhang CY, Liu XM, Zhou
WJ, et al. Effects of hydrogen sulfide on hypoxic pulmonary vascular
structural remodeling. Life Sci 2006; 78: 1299_309.
36 Wang YF, Shi L, Du JB, Tang CS. Impact of
L-arginine on hydrogen
sulfide/cystathionine-γ-lyase pathway in rats with high
blood flow-induced pulmonary hypertension. Biochem Biophys
Res Commun 2006; 345: 851_7.
37 Li XH, Du JB, Bu DF, Tang XY, Tang CS. Sodium hydrosulfide
alleviated pulmonary vascular structural remodeling induced by
high pulmonary blood flow in rats. Acta Pharmacol Sin 2006;
27: 977_86.
38 Zhong GZ, Chen FR, Cheng YQ, Tang CS, Du JB. The role of
hydrogen sulfide in the pathogenesis of hypertension in rats
induced by inhibition of nitric oxide synthase. J Hypertens 2003;
21:1879_85.
39 Kredich NM, Foote LJ, Keenan BS. The stoichiometry and
kinetics of the inducible cysteine desulfhydrase from Salmonella
typhimurium. J Biol Chem 1973; 248: 6187_96.
40 Wu SY, Pan CS, Geng B, Zhao J, Yu F, Pang
YZ, et al. Hydrogen sulfide ameliorates vascular calcification induced by vitamin D3
plus nicotine in rats. Acta Pharmacol Sin 2006; 27: 299_306.
41 Xiao L, Wu YM, Zhang H, Liu YX, He RR. Hydrogen sulfide
facilitates carotid sinus baroreflex in anesthetized rats. Acta
Pharmacol Sin 2006; 27: 294_8.
42 Olson KR, Dombkowski RA, Russell MJ, Doellman MM, Head
SK, Whitfield NL, et al. Hydrogen sulfide as an oxygen
sensor/transducer in vertebrate hypoxic vasoconstriction and hypoxic
vasodilation. J Exp Biol 2006; 209: 4011_23.
43 Zhang QY, Du JB, Zhou WJ, Yan H, Tang CS, Zhang CY. Impact
of hydrogen sulfide on carbon monoxide/heme oxygenase
pathway in the pathogenesis of hypoxic pulmonary hypertension.
Biochem Biophys Res Commun 2004; 317: 30_7.
44 Jin HF, Du JB, Li XH, Wang YF, Liang YF, Tang CS. Interaction
between hydrogen sulfide/cystathionine gamma-lyase and
carbon monoxide/heme oxygenase pathways in aortic smooth muscle
cells. Acta Pharmacol Sin 2006; 27: 1561_6.
45 Yan H, Du JB, Tang CS, Geng B, Jiang HF. Changes in arterial
hydrogen sulfide (H2S) content during septic shock and
endotoxin shock in rats. J Infect 2003; 47: 155_60.
46 Wang J, Hegele RA. Genomic basis of cystathioninuria (MIM
219500) revealed by multiple mutations in cystathionine
gamma-lyase (CTH). Hum Gene 2003; 112: 404_8.
47 Geng B, Yang J, Qi Y, Zhao J, Pang Y, Du
JB, et al. H2S generated
by heart in rat and its effects on cardiac function. Biochem
Biophys Res Commun 2004; 313: 362_8.
48 O'Rourke B. Pathophysiological and protective roles of
mitochondrial ion channels. J Physiol 2000; 529:
23_36.
49 Gross GJ, Fryer RM. Sarcolemmal versus mitochondrial
ATP-sensitive K+ channels and myocardial preconditioning. Circ Res
1999; 84: 973_9.
50 Pan TT, Feng ZN, Lee SW, Moore PK, Bian JS. Endogenous
hydrogen sulfide contributes to the cardioprotection by
metabolic inhibition preconditioning in the rat ventricular myocytes.
J Mol Cell Cardiol 2006; 40: 119_30.
51 Zhu YZ, Wang ZJ, Ho P, Loke YY, Zhu YC, Huang
XW, et al. Hydrogen sulfide and its cardioprotective effects in myocardial
ischemia in experimental rats. J Appl Physiol 2006; 102: 261_8.
52 Geng B, Chang L, Pan C, Qi Y, Zhao J, Pang
Y, et al. Endogenous hydrogen sulfide regulation of myocardial injury induced
by isoproterenol. Biochem Biophys Res Commun 2004; 318:
756_63.
53 Patacchini R, Santicioli P, Giuliani S, Maggi CA.
Pharmacological investigation of hydrogen sulfide
(H2S) contractile activity in rat detrusor muscle. Eur J Pharmacol 2005; 509:
171_7.
54 Maggi CA, Santicioli P, Giuliani S, Furio M, Meli A. The
capsaicin-sensitive innervation of the rat urinary bladder: further
studies on mechanisms regulating micturition threshold. J Urol 1986;
136: 696_700.
55 Birder LA, Apodaca G, De Groat WC, Kanai AJ. Adrenergic- and
capsaicin-evoked nitric oxide release from urothelium and
afferent nerves in urinary bladder. Am J Physiol 1998; 275:
226_9.
56 Maggi CA, Patacchini R, Giachetti A, Meli A. Tachykinin
receptors in the circular muscle of the guinea-pig ileum. Br J
Pharmacol1997; 101: 996_1000.
57 Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine
JD, Julius D. The capsaicin receptor: a heat-activated ion
channel in the pain pathway. Nature 1997; 389:
816_24.
58 Tominaga M, Numazaki M, Iida T, Moriyama T, Togashi K,
Higashi T, et al. Regulation mechanisms of vanilloid receptors.
Novartis Found Symp 2004; 261: 4_12.
59 Zygmunt PM, Julius I, Di Marzo I, Hogestatt ED.
Anandamide_the other side of the coin. Trends Pharmacol Sci 2000; 21:
43_4.
60 Hwang SW, Cho H, Kwak J, Lee SY, Kang CJ, Jung
J, et al. Direct activation of capsaicin receptors by products of lipoxygenases:
endogenous capsaicin-like substances. Proc Natl Acad Sci USA
2000; 97: 6155_60.
61 Huang SM, Bisogno T, Trevisani M, Al-Hayani A, De Petrocellis
L, Fezza F, et al. An endogenous capsaicin-like substance with
high potency at recombinant and native vanilloid VR1 receptors.
Proc Natl Acad Sci USA 2002; 99: 8400_5.
62 Wimalawansa SJ. Antihypertensive effects of oral calcium
supplementation may be mediated through the potent vasodilator CGRP.
Am J Hypertens 1993; 6: 996_1002.
63 Birder LA, Nakamura Y, Kiss S, Nealen ML, Barrick S, Kanai AJ,
et al. Altered urinary bladder function in mice lacking the vanilloid
receptor TRPV1. Nat Neurosci 2002; 5: 856_60.
64 Inoue K, Koizumi S, Fuziwara S, Denda S, Inoue K, Denda M.
Functional vanilloid receptors in cultured normal human
epidermal keratinocytes. Biochem Biophys Res Commun 2002; 291:
124_9.
65 Xin H, Tanaka H, Yamaguchi M, Takemori S, Nakamura A,
Kohama K. Vanilloid receptor expressed in the sarcoplasmic
reticulum of rat skeletal muscle. Biochem Biophys Res Commun
2005; 332: 756_62.
66 Trevisani M, Smart D, Gunthorpe MJ, Tognetto M, Barbieri M,
Campi B, et al. Ethanol elicits and potentiates nociceptor
responses via the vanilloid receptor-1. Nat Neurosci 2002; 5:
546_51.
67 Teague B, Asiedu S, Moore PK. The smooth muscle relaxant
effect of hydrogen sulphide in vitro: evidence for a physiological
role to control intestinal contractility. Br J Pharmacol 2002;
137: 139_45.
68 Li L, Bhatia M, Zhu YZ, Zhu YC, Ramnath RD, Wang
ZJ, et al. Hydrogen sulfide is a novel mediator of lipopolysaccharide-induced inflammation in the mouse. FASEB J 2005; 19: 1196_8.
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