Abstract
As we reported previously, intravenous administration of neurotensin (NT) produced triphasic blood pressure response, i.e. first depressor, second pressor and third depressor responses in pentobarbital anesthetized rats, and these responses were mediated by endogenous histamine (Japan. J. Pharmacol. 31, 1043, 1981 and Neuropeptides 2, 279, 1982). In the present study, we examined the mechanisms involved in NT tachyphylaxis. For 1 hour after the first injection of NT (1.67 μg/kg), NT tachyphylaxis was observed, but hypotensive effect of acetylcholine or serotonin was not affected. The hypotensive effect of NT was markedly attenuated by pretreatment with histamine. Inhibitors for prostaglandin synthesis, indomethacin, mefenamic acid and aspirin, reversed the tachyphylaxis to NT. In the indomethacin-treated rats, intravenous infusion of prostaglandin E2 again reduced the response on the second injection of NT. These results suggest that endogenous histamine and prostaglandin (s) participate in NT tachyphylaxis in rat blood pressure.
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