Cyclic GMP-independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor

Homer, KL and Wanstall, JC (2000) Cyclic GMP-independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor. British Journal of Pharmacology, 131 4: 673-682. doi:10.1038/sj.bjp.0703613


Author Homer, KL
Wanstall, JC
Title Cyclic GMP-independent relaxation of rat pulmonary artery by spermine NONOate, a diazeniumdiolate nitric oxide donor
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 2000-01-01
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0703613
Volume 131
Issue 4
Start page 673
End page 682
Total pages 10
Editor D.A. Brown
P.K. Moore
Place of publication Basingstoke, Hampshire, UK
Publisher Macmillan Publishers Ltd
Collection year 2000
Language eng
Subject C1
320502 Basic Pharmacology
730106 Cardiovascular system and diseases
Abstract 1 In rat pulmonary artery pre-contracted with phenylephrine, the mechanisms of relaxation to the nitric oxide (NO) donor, spermine NONOate, were investigated. 2 Responses to spermine NONOate were only partially blocked by the soluble guanylate cyclase inhibitor, ODQ (1H-[1,2,4]Oxadiazolo-[4,3,-a]quinoxalin-1-one) at concentrations up to 30 muM. Ten muM ODQ gave maximal inhibition. Endothelium removal had no effect on the potency of spermine NONOate or its inhibition by ODQ. 3 The protein kinase G inhibitor, Rp-8-Br-cGMPS (100 muM), caused minimal inhibition of spermine NONOate despite causing marked inhibition of glyceryl trinitrate and isosorbide dinitrate. 4 Spermine NONOate (100 muM) caused a 35 fold increase in guanosine 3'5' cyclic monophosphate (cyclic GMP) above basal levels in pulmonary artery rings. ODQ (3 muM) abolished this cyclic GMP production but did not inhibit corresponding relaxant responses. Similar results were seen with another NONOate (MAHMA NONOate; 10 muM). 5 ODQ-resistant relaxation to spermine NONOate (i.e. relaxation seen in the presence of 10 muM ODQ) was inhibited by potassium (80 mM), charybdotoxin (300 nM), iberiotoxin (300 nM), apamin (100 nM), ouabain (1 mM) or thapsigargin (100 nM) but not by 4-aminopyridine (3 mM), glybenclamide (10 muM) or diltiazem (10 muM). 6 Potassium, charybdotoxin, ouabain and thapsigargin also inhibited ODQ-resistant relaxation to FK409 ((+/-)-E-4-ethyl-2-[E-hydroxyimino]-5-nitro-3-hexenamide). 7 We conclude that, on rat pulmonary artery, spermine NONOate can produce cyclic GMP-independent relaxation that involves, at least in part, activation of Na+/K+-ATPase, sarco-endoplasmic reticulum Ca2+-ATPase and calcium-activated potassium channels.
Keyword Pharmacology & Pharmacy
Calcium-activated Potassium Channels
Cyclic Gmp-independent Relaxation
Fk409
Na+/k+-atpase
Nitric Oxide Donors
Rat Pulmonary Artery
Sarco-endoplasmic Reticulum Ca2+-atpase
Spermine Nonoate
Soluble Guanylyl Cyclase
Smooth-muscle Cells
1h-<1,2,4>oxadiazolo<4,3-a>quinoxalin-1-one Odq
Mesenteric-artery
K+ Channels
Inhibitor
Mechanisms
Activation
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Pharmacy Publications
 
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Created: Tue, 10 Jun 2008, 21:29:36 EST