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Prolonged relaxation consistent with persistent soluble guanylyl cyclase activation in canine pulmonary artery following brief treatment with nitric oxide donors

Authors
 Young L. Kwak  ;  Keith A. Jones  ;  David O. Warner  ;  William J. Perkins 
Citation
 LIFE SCIENCES, Vol.79(21) : 2001-2009, 2006 
Journal Title
LIFE SCIENCES
ISSN
 0024-3205 
Issue Date
2006
MeSH
Animals ; Cyclic GMP/metabolism ; Dogs ; Dose-Response Relationship, Drug ; Enzyme Activation/drug effects ; Female ; Guanylate Cyclase/metabolism* ; In Vitro Techniques ; Isometric Contraction/drug effects ; Male ; Nitric Oxide/metabolism* ; Nitric Oxide Donors/chemistry ; Nitric Oxide Donors/pharmacology* ; Pulmonary Artery/drug effects* ; Pulmonary Artery/enzymology ; Structure-Activity Relationship ; Time Factors ; Vasodilation/drug effects*
Keywords
Pulmonary artery ; Nitric oxide ; cGMP ; Soluble guanylyl cyclase ; Dithiothreitol
Abstract
Recent work has indicated that prolonged treatment with nitric oxide (NO) donors results in tissue storage of NO as S-nitrosothiols and N-nitrosamines. The possibility thus exists that NO treatment may result in the development of tissue stores of NO with functionally significant effects following removal of the original NO source. In these studies, the effects of 10 min treatment with two chemically distinct NO sources, S-nitrosoglutathione (GSNO) and (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NO) were determined in canine pulmonary artery using a superfusion system that permitted continuous isometric force recording during addition and removal of the NO donors. Relaxation that persisted for up to 1 h after removal of the NO source, was demonstrated for both NO sources, but at lower concentrations relative to the relaxant EC50 for GSNO versus DEA-NO. Persistent relaxation with both NO sources was fully reversed by both the sGC inhibitor, ODQ, and an inhibitor of cGMP-dependent protein kinase, Rp-8-Br-PET-cGMPS, indicating that persistent relaxation was consistent with persistent activation of the sGC-cGMP signaling pathway. In separate measurements, a GSNO-induced persistent increase in both tissue cGMP ([cGMP]i) and relaxation were fully reversed by both ODQ and the thiol reducing agent dithiothreitol (DTT). The results indicate that vascular smooth muscle is capable of converting short-lived NO responses following short term exposure to NO donors by a mechanism consistent with prolonged sGC activation, resulting in persistent relaxation. Reversal of this cGMP-dependent process with DTT suggests that it occurs via mechanisms that are thiol redox sensitive.
Full Text
http://www.sciencedirect.com/science/article/pii/S0024320506005029
DOI
10.1016/j.lfs.2006.06.035
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Kwak, Young Lan(곽영란) ORCID logo https://orcid.org/0000-0002-2984-9927
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/110260
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