Effect of the neurotensin receptor antagonist SR48692 on rat blood pressure modulation by neurotensin.

When administered as an intravenous injection in the pentobarbitone-anaesthetized rat, neurotensin (NT) elicits a biphasic depressor-pressor effect that can be evaluated by the mean arterial blood pressure (MABP). The first hypotensive phase elicited by low doses of NT is dependent on the interaction of NT with its specific receptors and may be mediated by the release of histamine, since it is prevented by oral pretreatment with the selective NT receptor antagonist SR 48692 and by intravenous pretreatment with a selective H1 receptor antagonist mepyramine. The hypertensive effect evoked by higher doses of NT is histamine-independent but remains NT receptor- mediated. The prevention of the biphasic effect on MABP by oral administration of the NT receptor antagonist SR 48692 validates the implication of NT receptors in the histamine release phenomenon.