Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate

Homer, K. L. and Wanstall, J. C. (2002) Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate. British Journal of Pharmacology, 137 7: 1071-1081. doi:10.1038/sj.bjp.0704971


Author Homer, K. L.
Wanstall, J. C.
Title Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate
Journal name British Journal of Pharmacology   Check publisher's open access policy
ISSN 0007-1188
Publication date 2002-12
Sub-type Article (original research)
DOI 10.1038/sj.bjp.0704971
Volume 137
Issue 7
Start page 1071
End page 1081
Total pages 11
Place of publication United Kingdom
Publisher Nature Publishing group
Collection year 2002
Language eng
Subject C1
320502 Basic Pharmacology
780105 Biological sciences
1115 Pharmacology and Pharmaceutical Sciences
Abstract 1 Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-{N-methyl-N-[6-(N-methylammoniohexyl)amino]}diazen-l-ium-1,2-diolate) was investigated. The aims were to compare its anti-aggregatory effect with vasorelaxation, to determine the effects of the soluble guanylate cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-ajquinoxalin-1-one), and to investigate the possible role of activation of sarco-encloplasmic reticulum calcium-ATPase (SERCA), independent of soluble guanylate cyclase, using thapsigargin. 2 MAHMA NONOate concentration-dependently inhibited sub-maximal aggregation responses to collagen (2 - 10 mug ml(-1)) and adenosine diphosphate (ADP; 2 mum) in platelet rich plasma. It was (i) more effective at inhibiting aggregation induced by collagen than by ADP, and (ii) less potent at inhibiting platelet aggregation than relaxing rat pulmonary artery. 3 ODQ (10 mum) caused only a small shift (approximately half a log unit) in the concentration-response curve to MAHMA NONOate irrespective of the aggregating agent. 4 The NO-independent activator of soluble guanylate cyclase, YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzy] indazole; 1 - 100 mum), did not inhibit aggregation. The cGMP analogue, 8-pCPT-cGMP (8-(4-chlorophenylthio)guanosine 3'5' cyclic monophosphate; 0.1 - 1 mm), caused minimal inhibition. 5 On collagen-aggregated platelets responses to MAHMA NONOate (ODQ 10 PM present) were abolished by thapsigargin (200 nm). On ADP-aggregated platelets thapsigargin caused partial inhibition. 6 Results with S-nitrosoglutathione (GSNO) resembled those with MAHMA NONOate. Glyceryl trinitrate and sodium nitroprusside were poor inhibitors of aggregation. 7 Thus inhibition of rat platelet aggregation by MAHMA NONOate (like GSNO) is largely ODQ-resistant and, by implication, independent of soluble guanylate cyclase. A likely mechanism of inhibition is activation of SERCA.
Keyword Pharmacology & Pharmacy
Mahma Nonoate
Nitric Oxide Donor Drugs
Odq
Odq-resistant Responses
Rat Platelet Aggregation
Sarco-endoplasmic Reticulum Calcium-atpase
Soluble Guanylate Cyclase Inhibitor
Soluble Guanylyl Cyclase
Vascular Smooth-muscle
In-vitro
Cyclic-gmp
Calcium Mobilization
Sodium-nitroprusside
Induced Relaxation
Pulmonary-artery
Ca2+
No
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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Created: Tue, 14 Aug 2007, 19:02:53 EST