Antidiuretic Effects of Neurotensin in Chloralose Anaesthetized Dogs

Abstract

1. Effects of cerebroventricular and/or intravenous infusions of neurotensin (NT), an endogenous tridecapeptide, on haemodynamics and renal function were investigated in chloralose anaesthetized dogs. 2. Cerebroventricular infusions (i.c.v.) of NT (10-6 mol/L and 10-5 mol/L, 0.1 mL/min) for 30 min did not produce any significant alterations in the measured variables. In the vagotomized dogs, intravenous (i.v.) infusion of NT (10(-5) mol/L) at a rate of 0.1 mL/min for 30 min significantly lowered the arterial blood pressure and glomerular filtration rate; these effects were accompanied by pronounced reductions in the urine flow and urinary sodium excretion and marked increases in urine osmolality. 3. In the dogs with vagi intact, i.v. infusions of NT failed to produce any alterations in the blood pressure; however, renal effects of NT were essentially identical to those observed in the vagotomized dogs. 4. Infusions of NT (10(-6) mol/L) and/or NT-metabolites NT1-8 and NT8-13 (10(-5) mol/L) directly into the renal artery failed to produce any significant alterations in the urine flow. Antidiuretic effects of i.v. NT were not prevented by acute renal denervation, adrenalectomy, or pretreatment of the animals with naloxone. However, morphine pretreatment completely abolished the hypotensive and anti-diuretic effects of NT. 5. It is proposed that i.v. infusion of NT rapidly facilitates the secretion of an endogenous substance possessing potent antidiuretic properties and opiate mechanisms are involved in mediating such an effect. Although it appears unlikely, a role for vasopressin cannot be ruled out.

Negative modulation of nitric oxide production by neurotensin as a putative mechanism of the diuretic action of SR 48692 in rats

“…NT has an antidiuretic action after i.v. infusion in several animal species (Unwin et al, 1987;Kivlighn & Jandhyala, 1990) and our ®ndings showing inhibition of diuresis in fasted, water-loaded rats given i.c.v. NT further support this.…”

“…It acts as a paracrine and endocrine modulator of digestive functions in the gut (Ferris, 1989). It is located in specific glandular cells, called the N cells, and may be released into the blood after food ingestion, thus influencing not only the digestive system (Mashford et al , 1978; Blackburn et al , 1980; Croci et al , 1995a), but presumably the cardiovascular system and renal functions too (Quirion et al , 1982; Bloom et al , 1983; Unwin et al , 1987; Kivlighn & Jandhyala, 1990; Nisato et al , 1994). NT has antidiuretic action after i.v.…”

Inhibition of atrial natriuretic peptide-induced natriuresis by plasma hydrolysates containing pepsanurin.

“…1 Particularly relevant is the case of neurotensin, which has antidiuretic properties, 20 although it apparently does not exert its action directly on the kidney. 21 In this context, it has been proposed that one or a combination of neurointestinal peptides may be part of a signaling mechanism influencing renal excretory rate, 21 * 22 and it seems pertinent to explore to what extent pepsanurin and its plasma precursor could be involved in this process.…”