Relatively selective neuronal nitric oxide synthase inhibition by 7-nitroindazole in monkey isolated cerebral arteries.
The selectivity of 7-nitroindazole in inhibiting endothelial and neuronal nitric oxide synthases (eNOS and nNOS) was investigated by comparing its inhibitory action on relaxations mediated by nitric oxide (NO) in response to stimulation of perivascular nerves and in response to histamine in monkey cerebral artery strips. 7-Nitroindazole at 2 x 10(-5) M moderately attenuated the response to transmural electrical stimulation and to nicotine, but did to alter the endothelium-dependent relaxation in response to histamine in cimetidine-treated strips. Raising the concentration of 7-nitroindazole to 10(-4) M abolished the neurogenic response, partially inhibited the histamine-induced relaxation, but did not affect the response to NO. It is concluded that 7-nitroindazole is a relatively selective nNOS inhibitor; however, at high concentrations, it inhibits eNOS in monkey cerebral arteries.
Ayajiki
K
K
Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu 520-2192, Japan.
Fujioka
H
H
Okamura
T
T
Toda
N
N
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D008251:Macaca; D009538:Nicotine / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D007191:Indazoles; D009569:Nitric Oxide; D009538:Nicotine; D006632:Histamine; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole