Influence of histamine and prostaglandin on desensitization to neurotensin in rat blood pressure.

Triphasic depressor-pressor-depressor blood pressure responses to neurotensin (NT: 1.67 micrograms/kg i.v.) in anesthetized rats were not elicited when the second dose of NT was administered 20 min after the first injection. Pretreatment of animals with histamine markedly reduced the depressor response to NT, and vice versa. The triphasic blood pressure pattern remained unaffected with acetylcholine and serotonin treatment, and hypotensive effects of acetylcholine and serotonin were not modified by NT. Attenuation of depressor response induced by the second injection of NT was antagonized by pretreatment with prostaglandin synthesis inhibitors such as indomethacin, mefenamic acid and acetylsalicylic acid. These results suggest that histamine and prostaglandins play a role in the development of desensitization to NT in rat blood pressure.