title: Hydrogen-sulfide-mediated vasodilatory effect of nucleoside 5'-monophosphorothioates in perivascular adipose tissue.
abstract: Hydrogen sulfide (H2S) is synthesized in perivascular adipose tissue (PVAT) and induces vasorelaxation. We examined whether the sulfur-containing AMP and GMP analogs AMPS and GMPS can serve as the H2S donors in PVAT. H2S production by isolated rat periaortic adipose tissue (PAT) was measured with a polarographic sensor. In addition, phenylephrine-induced contractility of aortic rings with (+) or without (-) PAT was examined. Isolated PAT produced H2S from AMPS or GMPS in the presence of the P2X7 receptor agonist BzATP. Phenylephrine-induced contractility of PAT(+) rings was lower than of PAT(-) rings. AMPS or GMPS had no effect on the contractility of PAT(-) rings, but used together with BzATP reduced the contractility of PAT(+) rings when endogenous H2S production was inhibited with propargylglycine. A high-fat diet reduced endogenous H2S production by PAT. Interestingly, AMPS and GMPS were converted to H2S by PAT of obese rats, and reduced contractility of PAT(+) aortic rings isolated from these animals even in the absence of BzATP. We conclude that (i) AMPS and GMPS can be hydrolyzed to H2S by PAT when P2X7 receptors are activated, (ii) a high-fat diet impairs endogenous H2S production by PAT, (iii) AMPS and GMPS restore the anticontractile effects of PAT in obese animals without P2X7 stimulation.
authors.affiliation: a Department of Pathophysiology, Medical University, ul. Jaczewskiego 8, 20-090 Lublin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Bełtowski
authors.affiliation: b Department of Biochemistry and Biotechnology, Poznań University of Life Sciences, Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Guranowski
authors.affiliation: c Department of Neurology, Medical University, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jamroz-Wiśniewska
authors.affiliation: d Department of Interventional Radiology and Neuroradiology, Medical University, Lublin, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wolski
authors.affiliation: d Department of Interventional Radiology and Neuroradiology, Medical University, Lublin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Hałas
mesh_terms: D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D017208:Rats, Wistar; D013873:Thionucleotides / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D013873:Thionucleotides; C014308:adenosine 5'-phosphorothioate; D000249:Adenosine Monophosphate; C066524:guanosine 5'-monophosphorothioate; D006157:Guanosine Monophosphate; D006862:Hydrogen Sulfide
keywords: HIT proteins; P2X7 receptors; high-fat diet; hydrogen sulfide; nucleoside phosphorothioates; obesity; obésité; perivascular adipose tissue; phosphorothioates nucléosidiques; protéines HIT; récepteurs purinergiques P2X7; régime à haute teneur en matières grasses; sulfure d’hydrogène; tissu adipeux périvasculaire; tonus vasculaire; vascular tone