Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo

Yuri Zagvazdin, Giuseppe Sancesario, Yi Xin Wang, Leonard Share, Malinda E.C. Fitzgerald, Anton Reiner

Research output: Contribution to journalArticle

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Abstract

We have examined whether the cardiovascular effects of 7-nitroindazole, a reportedly selective inhibitor of neuronal nitric oxide (NO) synthase, are induced without inhibition of endothelial NO synthase. A significant increase in mean arterial blood pressure but no change in heart rate was observed after 7-nitroindazole administration (50 mg/kg i.p.) in rats anesthetized with urethane or urethane and chloralose, while both an elevation in mean arterial blood pressure and bradycardia were observed in conscious animals after 7-nitroindazole administration (50 mg/kg i.p.). No enhancements in these effects on mean arterial blood pressure and heart rate were observed in urethane-chloralose anesthetized rats treated with a higher dose of 7-nitroindazole (75 mg/kg i.p.). Use of halothane to induce anesthesia abolished the pressor effect of 7-nitroindazole in rats studied under urethane anesthesia. 7-Nitroindazole shortened the duration of the acetylcholine (3 μg or 30 μg i.v.) but not the sodium nitroprusside (2 μg i.v.) induced hypotension in urethane-anesthetized rats. Pretreatment with L-arginine (300 mg/kg i.v.) inhibited the effects of 7-nitroindazole on mean arterial blood pressure and acetylcholine induced hypotension, suggesting involvement of the L-arginine-NO pathway in the effects of 7-nitroindazole. The effects of 7-nitroindazole on blood pressure and on the depressor responses to acetylcholine and sodium nitroprusside are similar to the effects previously observed after non-selective NO synthase inhibition by L-arginine analogs. Our results suggest, therefore, that 7-nitroindazole affects basal endothelial NO formation in vivo. The suppressive action of halothane on the cardiovascular effects of 7-nitroindazole suggests that the influence of anesthetics should be taken into consideration in studies of the cardiovascular effects of NO synthase inhibitors, particularly 7-nitroindazole.

Original languageEnglish (US)
Pages (from-to)61-69
Number of pages9
JournalEuropean Journal of Pharmacology
Volume303
Issue number1-2
DOIs
StatePublished - May 6 1996

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Nitric Oxide Synthase Type III
Arterial Pressure
Urethane
Controlled Hypotension
Acetylcholine
Arginine
Chloralose
Nitroprusside
Halothane
Nitric Oxide Synthase
7-nitroindazole
Nitric Oxide
Anesthesia
Heart Rate
Nitric Oxide Synthase Type I
Bradycardia
Anesthetics

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo. / Zagvazdin, Yuri; Sancesario, Giuseppe; Wang, Yi Xin; Share, Leonard; Fitzgerald, Malinda E.C.; Reiner, Anton.

In: European Journal of Pharmacology, Vol. 303, No. 1-2, 06.05.1996, p. 61-69.

Research output: Contribution to journalArticle

Zagvazdin, Yuri ; Sancesario, Giuseppe ; Wang, Yi Xin ; Share, Leonard ; Fitzgerald, Malinda E.C. ; Reiner, Anton. / Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo. In: European Journal of Pharmacology. 1996 ; Vol. 303, No. 1-2. pp. 61-69.
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