title: Vasoactivity of the gasotransmitters hydrogen sulfide and carbon monoxide in the chicken ductus arteriosus.
abstract: Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H(2)S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O(2) sensor. However, whether H(2)S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na(2)S (1 μM-1 mM), which forms H(2)S and HS(-) in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na(2)S elicited a 100% relaxation (pD(2) 4.02) of 21% O(2)-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na(2)S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K(+) channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, K(V)), glibenclamide (K(ATP)), iberiotoxin (BK(Ca)), TRAM-34 (IK(Ca)), and apamin (SK(Ca)). CO also relaxed O(2)-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by L-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and K(V) channel stimulation. The presence of inhibitors of H(2)S or CO synthesis as well as the H(2)S precursor L-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O(2) tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H(2)S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H(2)S or CO in the control of chicken ductal reactivity.
authors.affiliation: Department of Pediatrics, Maastricht University Medical Centre, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: van der Sterren
authors.forename: Pamela
authors.initials: P
authors.lastname: Kleikers
authors.forename: Luc J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Eduardo
authors.initials: E
authors.lastname: Villamor
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002248:Carbon Monoxide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D002642:Chick Embryo / Q000187:drug effects / Q000502:physiology*; D004373:Ductus Arteriosus / Q000187:drug effects* / Q000502:physiology; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D010455:Peptides; D013440:Sulfides; D014665:Vasodilator Agents; D019789:Tetraethylammonium; C064719:iberiotoxin; D002248:Carbon Monoxide; D015761:4-Aminopyridine; D010100:Oxygen; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; C033479:sodium sulfide; D006862:Hydrogen Sulfide