The hypotensive effect of centrally administered neurotensin in rats

We have evaluated the cardiovascular effects of intracerebroventricular (i.c.v.) injections of neurotensin (NT) in pentobarbital-anesthetized rats. In most animals, the i.c.v. injection of NT (5.4, 10.8 and 16.2 nmol/rat) induced a dose-dependent fall of the arterial blood pressure. This effect was usually rapid in onset (30-60 sec) and of short duration (approximately 1-4 min). It was not preceded nor accompanied by any significant alteration of the heart rate. In about 25% of the animals, the vasodepressor effect of i.c.v. injections of NT was long lasting (30-45 min). Conscious rats were much less sensitive than anesthetized animals. The hypotensive effects of intravenously (i.v.) administered NT was fully maintained in animals made tolerant to the hypotensive effect of centrally administered NT. Similarly, the animals made unresponsive to i.v. injections of NT either by repeated i.v. injections of NT (e.g. tachyphylaxis) or by a chronic treatment with compound 48/80, still responded normally to centrally administered NT. The results suggest the existence of at least two anatomically distinct sites of action through which NT can induce hypotension in rats. One appears to be located in the periphery and the other, in the central nervous system.