title: Hydrogen sulfide in the mouse ductus arteriosus: a naturally occurring relaxant with potential EDHF function.
abstract: We have previously reported that bradykinin relaxes the fetal ductus arteriosus via endothelium-derived hyperpolarizing factor (EDHF) when other naturally occurring relaxants (prostaglandin E2, nitric oxide, and carbon monoxide) are suppressed, but the identity of the agent could not be ascertained. Here, we have examined in the mouse whether hydrogen sulfide (H2S) is a relaxant of the ductus and, if so, whether it may also function as an EDHF. We found in the vessel transcripts for the H2S synthetic enzymes, cystathionine-γ-lyase (CSE) and cystathionine-β-synthase (CBS), and the presence of these enzymes was confirmed by immunofluorescence microscopy. CSE and CBS were distributed across the vessel wall with the former prevailing in the intimal layer. Both enzymes occurred within the endoplasmic reticulum of endothelial and muscle cells, whereas only CSE was located also in the plasma membrane. The isolated ductus contracted to inhibitors of CSE (d,l-propargylglycine, PPG) and CBS (amino-oxyacetic acid), and PPG contraction was attenuated by removal of the endothelium. EDHF-mediated bradykinin relaxation was curtailed by both PPG and amino-oxyacetic acid, whereas the relaxation to sodium nitroprusside was not affected by either treatment. The H2S donor sodium hydrogen sulfide (NaHS) was also a potent, concentration-dependent relaxant. We conclude that the ductus is endowed with a H2S system exerting a tonic relaxation. In addition, H2S, possibly via an overriding CSE source, qualifies as an EDHF. These findings introduce a novel vasoregulatory mechanism into the ductus, with implications for antenatal patency of the vessel and its transitional adjustments at birth.
authors: Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
authors: Barbara
authors: B
authors: Baragatti
authors: Enrica
authors: E
authors: Ciofini
authors: Daria
authors: D
authors: Sodini
authors: Stefano
authors: S
authors: Luin
authors: Francesca
authors: F
authors: Scebba
authors: Flavio
authors: F
authors: Coceani
mesh_terms: D000480:Alkynes / Q000494:pharmacology; D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004373:Ductus Arteriosus / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D032342:Muscle Cells / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic; D017539:Tunica Intima / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D014664:Vasodilation
chemical_list: D000480:Alkynes; D045462:Endothelium-Dependent Relaxing Factors; D012333:RNA, Messenger; D000625:Aminooxyacetic Acid; D009599:Nitroprusside; C009055:propargylglycine; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase; D001920:Bradykinin; D005998:Glycine; D006862:Hydrogen Sulfide