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The Effects of Nitric Oxide Synthase Inhibitors on the Sedative Effect of Clonidine

2001; Lippincott Williams & Wilkins; Volume: 93; Issue: 5 Linguagem: Inglês

10.1097/00000539-200111000-00035

1526-7598

Roberto Soares de Moura, Anna Amélia S. Rios, Luiz Fernando de Oliveira, Ângela Castro Resende, Miguel de Lemos Neto, Edmar J. A. Santos, Marcelo Correia, Tania Tano,

Nitric Oxide and Endothelin Effects

The mechanism underlying the Niteroi, Rio de Janeiro sedative effect of clonidine, an α2-adrenoceptor agonist, remains uncertain. Because activation of α2-adrenoceptors induces release of nitric oxide (NO), we tested the hypothesis that the sedative effect of clonidine depends on NO-related mechanisms. The effect of 7-nitro indazole on the sleeping time induced by clonidine was studied in Wistar rats. In addition, we examined the effect of clonidine, α-methyldopa, and midazolam on the thiopental-induced sleeping time in rats pretreated with NG-nitro-l-arginine-methyl-esther (l-NAME). The sleeping time induced by clonidine was significantly decreased by 7-nitro indazole. Thiopental sleeping time was increased by clonidine, α-methyldopa, and midazolam. l-NAME reduced the prolongation effect of clonidine and α-methyldopa, but did not alter the effect of midazolam on the thiopental-induced sleeping time. The inhibitory effect of l-NAME on clonidine-dependent prolongation of thiopental-induced sleeping time was reversed by l-arginine. These results suggest that NO-dependent mechanisms are involved in the sedative effect of clonidine. In addition, this effect seems to be specific for the sedative action of α2-adrenoceptors agonists.