Platelet inhibitory effects of the nitric oxide donor drug MAHMA NONOate in vivo in rats

• Published in: European journal of pharmacology Vol. 482; no. 1; pp. 265 - 270
• Main Authors: Homer, Kerry L, Wanstall, Janet C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 15-12-2003; Elsevier
• Subjects: Animals; Biological and medical sciences; Blood Platelets - cytology; Blood Platelets - drug effects; Blood Platelets - physiology; Blood Pressure - drug effects; Blood Pressure - physiology; Dose-Response Relationship, Drug; Hydrazines - pharmacology; in vivo; MAHMA NONOate; Male; Medical sciences; Nitric oxide (NO) donors; Nitric Oxide Donors - pharmacology; Pharmacology. Drug treatments; Platelet Aggregation Inhibitors - pharmacology; Platelet inhibition; Rats; Rats, Wistar; S-nitrosoglutathione; Vasodepression systemic; MAHMA NONOate; Platelet inhibition; Nitric oxide (NO) donors; S-nitrosoglutathione; Vasodepression systemic; Drug; In vivo; Vertebrata; Platelet; Mammalia; Rat; Animal; Nitric oxide; Rodentia; in vivo; MAHMA NONOate; Nitric oxide (NO) donors; S-nitrosoglutathione; Vasodepression systemic
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.10.016

The platelet inhibitory effects of the nitric oxide (NO) donor drug MAHMA NONOate ((
Z-1-{
N-methyl-
N-[6-(
N-methylammoniohexyl)amino]}diazen-1-ium-1,2-diolate) were examined in anaesthetised rats and compared with those of
S-nitrosoglutathione (GSNO; an
S-nitrosothiol). Bolus administration of the aggregating agent ADP dose-dependently reduced the number of circulating free platelets. Intravenous infusions of MAHMA NONOate (3–30 nmol/kg/min) dose-dependently inhibited the effect of 0.3 μmol/kg ADP. MAHMA NONOate was approximately 10-fold more potent than GSNO. MAHMA NONOate (0.3–10 nmol/kg/min) also reduced systemic artery pressure and was again 10-fold more potent than GSNO. Thus MAHMA NONOate has both platelet inhibitory and vasodepressor effects in vivo. The dose ranges for these two effects overlapped, although blood pressure was affected at slightly lower doses. The platelet inhibitory effects compared favourably with those of GSNO, even though NONO-ates generate free radical NO which, in theory, could have been scavenged by haemoglobin. Therefore platelet inhibition may be a useful therapeutic property of NONOates.