Hypotensive effects of centrally and peripherally administered neurotensin and neurotensin derivatives in rats

Quirion, Rémi; Rioux, Francis; St‐Pierre, Serge; Bélanger, F.; Jolicoeur, F.B.; Barbeau, A.

doi:10.1016/0143-4179(81)90003-2

Cited by 39 publications

(6 citation statements)

References 7 publications

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“…[D-TrP"l-neurotensin (n=5) had no effect on the dynamics of sinus arrhythmia. This agrees with previous data that modification of the NT molecule by substituting 10-13 amino acid residues considerably reduces the peptide activity [7,8].…”

Section: Resultssupporting

confidence: 92%

Effect of neurotensin and epinephrine on sinus arrhythmia caused by burst stimulation of the vagus nerve

et al. 1997

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Administration of neurotensin against the background of sinus arrhythmia caused by burst stimulation of the vagus nerve in cats restores synchronization of the cardiac and vagal rhythms or modulates the proportion between them. This either stops the arrhythmia or changes its parameters. The effects of the peptide are similar to those of epinephrine and are abolished by 13-adrenoreceptor blockage. Key Words: vagus nerve; sinus arrhythmia; neurotensin; epinephrineThe effect of the vagus nerve (VN) on the heart is modulated by peptides localized in neurons of the intracardial nervous system [2,9], For instance, neurotensin (NT) considerably changes the dynamics of controlled bradycardia caused by synchronization of the cardiac rhythm with the frequency of bursts delivered to the VN [3]. The aim of the present study was to investigate the effect of this peptide under conditions of desynchronization of the vagal and cardiac rhythms, in particular in sinus arrhythmia [4]. MATERIALS AND METHODSExperiments were carried out on 22 cats weighing 2.5-3.5 kg narcotized intraperitoneally with a Chloralose-Nembutal mixture (75 and 15 mg/kg, respectively), and artificially ventilated. The right VN was divided in the neck and its peripheral end was stimulated by bursts of 6 square pulses. The duration and frequency of the pulses in a burst were 2 msec and 40 Hz; the amplitude was 5-6 threshold values. The amplified ECG was recorded by means of a unipolar probe inserted through the femoral vein into the right atrium; the P wave of the ECG triggers the RESULTSThe duration of the cardiac cycle after dissection of the fight VN was 329.4+9.8 msec. Stimulation of VN resulted in bradycardia; within a certain range of burst repetition rate (from 1.44+0.09 to 1.78+0.1 Hz) the heartbeats became synchronous with the vagal stimuli (Fig. 1) allowing for strictly controlled modulation of the cardiac cycle duration (from 557.1+15.4 to 694.3+18.2 msec). These limits were specified as the upper and lower boundaries of the synchronization interval. A repetition rate exceeding this interval led to desynchronization and development of sinus arrhythmia. Sinus arrhythmia arose from disturbed parallelism between the repetition rate of bursts delivered to VN and the lengthened heart rate, so that position of the vagal stimulus varied from cycle to cycle. For instance, in above-synchronization arrhythmia, the burst repetition rate exceeded the heart rate and the next vagal stimulus

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Section: Resultssupporting

confidence: 92%

Effect of neurotensin and epinephrine on sinus arrhythmia caused by burst stimulation of the vagus nerve

et al. 1997

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“…14 Injections of substance P into the nucleus tractus solitarius of anesthetized rats resulted in hypotension, 21 whereas central injections of the peptide in conscious rats are normally pressor. 14 In our experiments with conscious animals, neurotensin always gave a pressor response, whereas, in the studies where neurotensin was depressor, 20 -2I animals were pentobarbitone anesthetized and so sympathetic activity was reduced.…”

Section: Discussionmentioning

confidence: 99%

Central pressor action of neurotensin in conscious rats.

Sumners¹,

Phillips²,

Richards³

1982

Hypertension

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SUMMARY The effects of neurotensin upon blood pressure in conscious rats were examined after intracerebroventricular (i.v.t.) or intravenous (i.v.) administration of this peptide. Whereas i.v. injected neurotensin (0.1-2.0 /u.g/kg) was depressor, i.v.t. injected neurotensin (1 fig and above) was pressor. Peripheral depressor responses could not be repeated in the same animal due to tachyphylaxis, but central pressor responses were repeatable without reduction in magnitude, showing that the two effects were separate entities. Thyrotropin-releasing hormone (TRH), which is reported to be a potent neurotensin antagonist, completely abolished the neurotensin depressor response, and attenuated the central pressor action. TRH did not alter the central pressor effect of another peptide, angiotensin II (All). The potent AH receptor antagonist saralasin, while abolishing the central pressor effect of AH, was completely without effect upon the neurotensin-induced pressor response. These results indicate that i.v.t. injected neurotensin and AH stimulate a rise in blood pressure via different receptors. The alpha-adrenergic antagonists phentolamine, prazosin, or yohimbine (injected i.v.t.) were able to abolish or attenuate the pressor response due to i.v.t.-injected neurotensin, suggesting involvement of the sympathetic nervous system in this response. These results are discussed in relation to the central pressor actions of other neuropeptides. (Hypertension 4: 888-893, 1982) KEY WORDS • blood pressure • neurotensin • angiotensin II thyrotropin releasing hormone * alpha adrenergic antagonists N EUROTENSIN is a basic tridecapeptide that was first isolated from bovine hypothalami. 1 This peptide is now known to be widespread in the central nervous system (CNS), 2 -3 and peripherally. -3 Neurotensin has fulfilled many of the criteria for being recognized as a CNS neurotransmitter, 3 and has many actions in the CNS. Such actions include its pronounced hypothermic effect after intracranial administration, and its marked enhancement of pentobarbital sleeping time. 4 Peripherally, neurotensin modulates glucoregulatory systems, leading to hyperglycemia or hyperglucagonemia. 5 In the blood it is a very potent hypotensive agent. ' The findings that other neurbactive peptides such as angiotensin II (All), substance P, enkephalin, and bradykinin are pressor agents when administered centrally to conscious rats, 6 " 9 and that bradykinin causes hypotension after peripheral administration, 10 led us investigate the effects of centrally administered neurotensin upon arterial blood pressure. These experiments were performed with the following aims: 1) to compare the blood pressure actions of neurotensin with those of other neuropeptides; 2) to determine whether the peripheral depressor effect of neurotensin contains a central component; and 3) to understand the mechanisms involved in the central vascular actions of neurotensin.Methods In all experiments, the animals used were male 250 to 300 g Sprague-Dawley rats. Animals were anesthe...

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“…The NT,-,, fragment may undergo a more rapid enzymatic degradation following its central administration effectively reducing the amount that may reach the target tissue. Consistent with these observations, centrally administered NT8-13 was found to be less potent than centrally administered NT in producing hypotension in phenobarbitol-anesthetized rats (51). Overall, both NT and NT,-,, activated the HPA axis while NT,-* failed to increase either ACTH or B.…”

Section: Discussionmentioning

confidence: 61%

“…The differences observed in ACTH and B levels between NT,-,, and the parent molecule, may reflect differences in the pharmacodynamic properties of these two peptides. Differences in the metabolism of these two peptides have already been reported following their central and peripheral administration (20,46,51,52). The NT,-,, fragment may undergo a more rapid enzymatic degradation following its central administration effectively reducing the amount that may reach the target tissue.…”

Section: Discussionmentioning

confidence: 95%

Stimulation of CRH‐Mediated ACTH Secretion by Central Administration of Neurotensin: Evidence for the Participation of the Paraventricular Nucleus

Rowe

Viau

Meaney

et al. 1995

J Neuroendocrinology

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Central administration of neurotensin (NT) stimulates hypothalamic-pituitary-adrenal (HPA) activity in freely-moving rats. Increases in adrenocorticotropin hormone (ACTH) and corticosterone (B) were observed 15 min following central NT administration and remained elevated for up to 4 h. Of the two NT fragments tested, NT1-8 and NT8-13, only NT8-13 was found to significantly elevate ACTH and B levels. Moreover, NT8-13 activated the HPA axis with a temporal profile similar to NT1-13, suggesting an interaction with the pharmacologically and molecularly characterized NT receptor. Animals pre-treated intravenously with the corticotropin-releasing hormone (CRH) antagonist, alpha-helical CRH, showed attenuated plasma ACTH and B responses to central NT administration. This indicates that CRH receptor activation is necessary for the stimulatory effects of NT on HPA function. Bilateral lesions of the paraventricular nucleus (PVN) of the hypothalamus significantly reduced NT-induced stimulation of ACTH and B release suggesting that the PVN is essential for NT's stimulatory action. Median eminence content studies indicated that acute central NT administration stimulates CRH, but not arginine vassopressin (AVP), release in animals examined 60 min following NT injection. Taken together, these findings suggest that the stimulatory effects of NT on HPA activity occur via specific NT receptors and that one site of action of NT is likely at the level of the PVN where NT elicits the release of CRH.

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Hypotensive effects of centrally and peripherally administered neurotensin and neurotensin derivatives in rats

Cited by 39 publications

References 7 publications

Effect of neurotensin and epinephrine on sinus arrhythmia caused by burst stimulation of the vagus nerve

Effect of neurotensin and epinephrine on sinus arrhythmia caused by burst stimulation of the vagus nerve

Central pressor action of neurotensin in conscious rats.

Stimulation of CRH‐Mediated ACTH Secretion by Central Administration of Neurotensin: Evidence for the Participation of the Paraventricular Nucleus

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