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.
Zagvazdin, Y., Sancesario, G., Wang, Y., Share, L., Fitzgerald, M., Reiner, A. (1996). Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo. EUROPEAN JOURNAL OF PHARMACOLOGY, 303(1-2), 61-69.
Evidence from its cardiovascular effects that 7-nitroindazole may inhibit endothelial nitric oxide synthase in vivo
SANCESARIO, GIUSEPPE;
1996-05-06
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 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
