Inhibition of rat platelet aggregation by the diazeniumdiolate nitric oxide donor MAHMA NONOate
| Autor: | Janet C. Wanstall, Kerry L. Homer |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Indazoles Thapsigargin SERCA Platelet Aggregation Enzyme Activators In Vitro Techniques Pulmonary Artery Pharmacology Nitric oxide S-Nitrosoglutathione chemistry.chemical_compound Quinoxalines medicine Animals Nitric Oxide Donors Enzyme Inhibitors Rats Wistar Cyclic GMP Oxadiazoles Dose-Response Relationship Drug Superoxide Dismutase Thionucleotides Catalase Rats Adenosine Diphosphate Adenosine diphosphate Hydrazines chemistry Biochemistry Guanylate Cyclase Vasoconstriction Papers Platelet aggregation inhibitor Collagen Sodium nitroprusside Soluble guanylyl cyclase Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | British Journal of Pharmacology. 137:1071-1081 |
| ISSN: | 0007-1188 |
| DOI: | 10.1038/sj.bjp.0704971 |
| Popis: | 1. Inhibition of rat platelet aggregation by the nitric oxide (NO) donor MAHMA NONOate (Z-1-N-methyl-N-[6-(N-methylammoniohexyl)amino]diazen-1-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-a]quinoxalin-1-one), and to investigate the possible role of activation of sarco-endoplasmic 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 micro g ml(-1)) and adenosine diphosphate (ADP; 2 micro M) 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 micro M) 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-benzyl indazole; 1-100 micro M), 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 micro M 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|