47
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Hydrogen sulfide and the vasculature: a novel vasculoprotective entity and regulator of nitric oxide bioavailability?

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Hydrogen sulfide (H 2S) is a well known and pungent toxic gas that has recently been shown to be synthesised in man from the amino acids cystathionine, homocysteine and cysteine by at least two distinct enzymes; cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H 2S has emerged as a novel and increasingly important mediator in the cardiovascular system but delineating the precise physiology and pathophysiology of H 2S is proving to be complex and difficult to unravel with disparate findings reported with cell types, tissue types and animal species reported. Therefore, in this review we summarize the mechanisms by which H 2S has been proposed to regulate blood pressure and cardiac function, discuss the mechanistic discrepancies reported in the literature as well as the therapeutic potential of H 2S. We also examine the methods of H 2S detection in biological fluids, processes for H 2S removal and discuss the reported blood levels of H 2S in man and animal models of cardiovascular pathology. We also highlight the complex interaction of H 2S with nitric oxide in regulating cardiovascular function in health and disease.

          Related collections

          Most cited references119

          • Record: found
          • Abstract: found
          • Article: not found

          H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase.

          Studies of nitric oxide over the past two decades have highlighted the fundamental importance of gaseous signaling molecules in biology and medicine. The physiological role of other gases such as carbon monoxide and hydrogen sulfide (H2S) is now receiving increasing attention. Here we show that H2S is physiologically generated by cystathionine gamma-lyase (CSE) and that genetic deletion of this enzyme in mice markedly reduces H2S levels in the serum, heart, aorta, and other tissues. Mutant mice lacking CSE display pronounced hypertension and diminished endothelium-dependent vasorelaxation. CSE is physiologically activated by calcium-calmodulin, which is a mechanism for H2S formation in response to vascular activation. These findings provide direct evidence that H2S is a physiologic vasodilator and regulator of blood pressure.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The vasorelaxant effect of H(2)S as a novel endogenous gaseous K(ATP) channel opener.

            Hydrogen sulfide (H(2)S) has been traditionally viewed as a toxic gas. It is also, however, endogenously generated from cysteine metabolism. We attempted to assess the physiological role of H(2)S in the regulation of vascular contractility, the modulation of H(2)S production in vascular tissues, and the underlying mechanisms. Intravenous bolus injection of H(2)S transiently decreased blood pressure of rats by 12- 30 mmHg, which was antagonized by prior blockade of K(ATP) channels. H(2)S relaxed rat aortic tissues in vitro in a K(ATP) channel-dependent manner. In isolated vascular smooth muscle cells (SMCs), H(2)S directly increased K(ATP) channel currents and hyperpolarized membrane. The expression of H(2)S-generating enzyme was identified in vascular SMCs, but not in endothelium. The endogenous production of H(2)S from different vascular tissues was also directly measured with the abundant level in the order of tail artery, aorta and mesenteric artery. Most importantly, H(2)S production from vascular tissues was enhanced by nitric oxide. Our results demonstrate that H(2)S is an important endogenous vasoactive factor and the first identified gaseous opener of K(ATP) channels in vascular SMCs.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide.

              Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously in mammalian tissues from L-cysteine mainly by two pyridoxal-5'-phosphate-dependent enzymes, cystathionine beta-synthetase and cystathionine gamma-lyase. Recently, we showed that cystathionine beta-synthetase in the brain produces H2S, and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing NMDA receptor activity. Here we show that mRNA for another H2S producing enzyme, cystathionine gamma-lyase, is expressed in the ileum, portal vein, and thoracic aorta. The ileum also expresses cystathionine beta-synthetase mRNA. These tissues produce H2S, and this production is blocked by cystathionine beta-synthetase and cystathionine gamma-lyase specific inhibitors. Although exogenously applied H2S alone relaxed these smooth muscles, much lower concentrations of H2S greatly enhanced the smooth muscle relaxation induced by NO in the thoracic aorta. These observations suggest that the endogenous H2S may regulate smooth muscle tone in synergy with NO.
                Bookmark

                Author and article information

                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                jcmm
                Journal of Cellular and Molecular Medicine
                Blackwell Publishing Ltd (Oxford, UK )
                1582-1838
                1582-4934
                March 2009
                24 March 2009
                : 13
                : 3
                : 488-507
                Affiliations
                [a ]Institute of Biomedical and Clinical Science, Peninsula Medical School, St. Luke's Campus, Exeter, UK
                [b ]Pharmaceutical Science Division, King's College London, London, UK
                Author notes
                *Correspondence to: Dr. Matt WHITEMAN, Institute of Biomedical and Clinical Science, Peninsula Medical School, St. Luke's Campus, Magdalen Road, Exeter, EX1 2LU, UK. Tel.: +44 (0) 1392 262942; Fax: +44 (0) 1392 262926 E-mail: matt.whiteman@ 123456pms.ac.uk ; m.whiteman@ 123456exeter.ac.uk
                Article
                10.1111/j.1582-4934.2009.00645.x
                3822510
                19374684
                5dc89a26-becc-47c2-afe5-198a4f0695e2
                © 2009 The Authors Journal compilation © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd
                History
                : 12 September 2008
                : 17 December 2008
                Categories
                Reviews

                Molecular medicine
                nitrosothiol,cardioprotection,katp,vasodilator,gaseous mediators,reactive nitrogen species,sulfur

                Comments

                Comment on this article