Relatively selective neuronal nitric oxide synthase inhibition by 7-nitroindazole in monkey isolated cerebral arteries

被引:33
作者
Ayajiki, K [1 ]
Fujioka, H [1 ]
Okamura, T [1 ]
Toda, N [1 ]
机构
[1] Shiga Univ Med Sci, Dept Pharmacol, Otsu, Shiga 52021, Japan
关键词
nitric oxide (NO); nitric oxide synthase (NOS) inhibitor; vasodilator nerve; cerebral artery; (monkey);
D O I
10.1016/S0014-2999(01)01068-8
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:179 / 183
页数:5
相关论文
共 20 条
[1]   INVOLVEMENT OF NITRIC-OXIDE IN ENDOTHELIUM-DEPENDENT, PHASIC RELAXATION CAUSED BY HISTAMINE IN MONKEY CEREBRAL-ARTERIES [J].
AYAJIKI, K ;
OKAMURA, T ;
TODA, N .
JAPANESE JOURNAL OF PHARMACOLOGY, 1992, 60 (04) :357-362
[2]   INHIBITION OF RAT CEREBELLAR NITRIC-OXIDE SYNTHASE BY 7-NITRO INDAZOLE AND RELATED SUBSTITUTED INDAZOLES [J].
BABBEDGE, RC ;
BLANDWARD, PA ;
HART, SL ;
MOORE, PK .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 110 (01) :225-228
[3]   ISOFORMS OF NITRIC-OXIDE SYNTHASE - CHARACTERIZATION AND PURIFICATION FROM DIFFERENT CELL-TYPES [J].
FORSTERMANN, U ;
SCHMIDT, HHHW ;
POLLOCK, JS ;
SHENG, H ;
MITCHELL, JA ;
WARNER, TD ;
NAKANE, M ;
MURAD, F .
BIOCHEMICAL PHARMACOLOGY, 1991, 42 (10) :1849-1857
[4]  
FURCHGOTT R F, 1988, P401
[5]  
Moncada S, 1997, PHARMACOL REV, V49, P137
[6]   7-NITRO INDAZOLE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, EXHIBITS ANTINOCICEPTIVE ACTIVITY IN THE MOUSE WITHOUT INCREASING BLOOD-PRESSURE [J].
MOORE, PK ;
BABBEDGE, RC ;
WALLACE, P ;
GAFFEN, ZA ;
HART, SL .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 108 (02) :296-297
[7]   CHARACTERIZATION OF THE NOVEL NITRIC-OXIDE SYNTHASE INHIBITOR 7-NITRO INDAZOLE AND RELATED INDAZOLES - ANTINOCICEPTIVE AND CARDIOVASCULAR EFFECTS [J].
MOORE, PK ;
WALLACE, P ;
GAFFEN, Z ;
HART, SL ;
BABBEDGE, RC .
BRITISH JOURNAL OF PHARMACOLOGY, 1993, 110 (01) :219-224
[8]   Neural mechanism of pressor action of nitric oxide synthase inhibitor in anesthetized monkeys [J].
Okamura, T ;
Ayajiki, K ;
Toda, N .
HYPERTENSION, 1996, 28 (03) :341-346
[9]   On the selectivity of 7-nitroindazole as an inhibitor of neuronal nitric oxide synthase [J].
Rainer, A ;
Zagvazdin, Y .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1998, 19 (09) :348-350
[10]   INCREASED STRIATAL DOPAMINE EFFLUX IN-VIVO FOLLOWING INHIBITION OF CEREBRAL NITRIC-OXIDE SYNTHASE BY THE NOVEL MONOSODIUM SALT OF 7-NITRO INDAZOLE [J].
SILVA, MT ;
ROSE, S ;
HINDMARSH, JG ;
AISLAITNER, G ;
GORROD, JW ;
MOORE, PK ;
JENNER, P ;
MARSDEN, CD .
BRITISH JOURNAL OF PHARMACOLOGY, 1995, 114 (02) :257-258