Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo
| Autor: | Leonard Share, Yuri Zagvazdin, Giuseppe Sancesario, Yi-Xin Wang, Malinda E.C. Fitzgerald, Anton Reiner |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Male
Indazoles 7-Nitroindazole Vasodilator Agents Hemodynamics Blood Pressure Pharmacology Arginine Rats Sprague-Dawley chemistry.chemical_compound Heart Rate medicine Animals Enzyme Inhibitors biology Chloralose Acetylcholine Rats Nitric oxide synthase Blood pressure chemistry Anesthesia biology.protein Endothelium Vascular Sodium nitroprusside Nitric Oxide Synthase Halothane medicine.drug |
| Zdroj: | European Journal of Pharmacology. 303:61-69 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(96)00106-9 |
| Popis: | 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 micrograms or 30 micrograms i.v.) but not the sodium nitroprusside (2 micrograms 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. |
| Databáze: | OpenAIRE |
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