Τίτλος:
Involvement of 3′,5′-cyclic inosine monophosphate in cystathionine γ-lyase-dependent regulation of the vascular tone
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background and Purpose: l-cysteine or hydrogen sulfide (H2S) donors induce a biphasic effect on precontracted isolated vessels. The contractile effect occurs within a concentration range of 10 nM to 3 μM followed by vasodilatation at 30–100 μM. Here, we have investigated the signalling involved in the H2S-induced contraction. Experimental Approach: Vascular response to NaHS or l-cysteine is evaluated on isolated precontracted with phenylephrine vessel rings harvested from wild type, cystathionine γ-lyase (CSE−/−), soluble guanylyl cyclase (sGCα1−/−) and endothelial nitric oxide synthase (eNOS−/−) knock-out mice. The cAMP, cGMP and inosine 3′,5′-cyclic monophosphate (cIMP) levels are simultaneously quantified using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) analysis. The involvement of sGC, phosphodiesterase (PDE) 4A and PDE5 are also evaluated. Key Results: CSE-derived H2S-induced contraction requires an intact eNOS/NO/sGC pathway and involves cIMP as a second messenger. H2S contractile effect involves a transient increase of cGMP and cAMP metabolism caused by PDE5 and PDE4A, thus unmasking cIMP contracting action. The stable cell-permeable analogue of cIMP elicits concentration-dependent contraction on a stable background tone induced by phenylephrine. The lack of cIMP, coupled to the hypocontractility displayed by vessels harvested from CSE−/− mice, confirms that H2S-induced contraction involves cIMP. Conclusion and Implications: The endothelium dynamically regulates vessel homeostasis by modulating contractile tone. This also involves CSE-derived H2S that is mediated by cIMP. © 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.
Συγγραφείς:
Mitidieri, E.
Vellecco, V.
Brancaleone, V.
Vanacore, D.
Manzo, O.L.
Martin, E.
Sharina, I.
Krutsenko, Y.
Monti, M.C.
Morretta, E.
Papapetropoulos, A.
Caliendo, G.
Frecentese, F.
Cirino, G.
Sorrentino, R.
d'Emmanuele di Villa Bianca, R.
Bucci, M.
Περιοδικό:
British Journal of Pharmacology
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
cyclic IMP; cystathionine gamma lyase; guanylate cyclase; hydrogen sulfide; nitric oxide synthase; phosphodiesterase IV; phosphodiesterase V; cyclic GMP; cystathionine gamma lyase; hydrogen sulfide; inosine phosphate; nitric oxide, adult; animal experiment; animal model; Article; C57BL 6 mouse; carotid artery; controlled study; electrospray mass spectrometry; Fourier transform mass spectrometry; high performance liquid chromatography; immunoblotting; in vitro study; liquid chromatography-mass spectrometry; major clinical study; male; mouse; nonhuman; proton nuclear magnetic resonance; reversed phase high performance liquid chromatography; thoracic aorta; ultra performance liquid chromatography; vasodilatation; Western blotting; wild type; animal; liquid chromatography; tandem mass spectrometry, Animals; Chromatography, Liquid; Cyclic GMP; Cystathionine gamma-Lyase; Hydrogen Sulfide; Inosine Monophosphate; Mice; Nitric Oxide; Tandem Mass Spectrometry
