Platelet inhibitory effects of the nitric oxide donor drug MAHMA NONOate in vivo in rats.
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 micromol/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.
Homer
Kerry L
KL
Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane Qld 4072, Australia.
Wanstall
Janet C
JC
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology*; D008297:Male; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C105785:1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; D006834:Hydrazines; D020030:Nitric Oxide Donors; D010975:Platelet Aggregation Inhibitors