Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jan;105(1):191–201. doi: 10.1111/j.1476-5381.1992.tb14234.x

Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats.

H Bachelard 1, S M Gardiner 1, P A Kemp 1, T Bennett 1
PMCID: PMC1908610  PMID: 1596682

Abstract

1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg-1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves.

Full text

PDF
191

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bachelard H., St-Pierre S., Rioux F. Participation of capsaicin-sensitive neurons in the cardiovascular effects of neurotensin in guinea pigs. Peptides. 1987 Nov-Dec;8(6):1079–1087. doi: 10.1016/0196-9781(87)90140-9. [DOI] [PubMed] [Google Scholar]
  2. Bachelard H., St-Pierre S., Rioux F. The chronotropic action of neurotensin in the guinea pig isolated heart. Peptides. 1985 Sep-Oct;6(5):841–845. doi: 10.1016/0196-9781(85)90311-0. [DOI] [PubMed] [Google Scholar]
  3. Bennett T., Kemp P. A. Lack of evidence for a temperature-mediated change of adrenoceptor type in the rat heart. Naunyn Schmiedebergs Arch Pharmacol. 1978 Jan-Feb;301(3):217–222. doi: 10.1007/BF00507040. [DOI] [PubMed] [Google Scholar]
  4. Bissette G., Manberg P., Nemeroff C. B., Prange A. J., Jr Neurotensin, a biologically active peptide. Life Sci. 1978 Nov 27;23(22):2173–2182. doi: 10.1016/0024-3205(78)90201-1. [DOI] [PubMed] [Google Scholar]
  5. Brown D. R., Miller R. J. Neurotensin. Br Med Bull. 1982 Sep;38(3):239–245. doi: 10.1093/oxfordjournals.bmb.a071767. [DOI] [PubMed] [Google Scholar]
  6. Carraway R., Bhatnagar Y. M. Isolation, structure and biologic activity of chicken intestinal neurotensin. Peptides. 1980 Summer;1(2):167–174. doi: 10.1016/0196-9781(80)90082-0. [DOI] [PubMed] [Google Scholar]
  7. Carraway R., Cochrane D. E., Lansman J. B., Leeman S. E., Paterson B. M., Welch H. J. Neurotensin stimulates exocytotic histamine secretion from rat mast cells and elevates plasma histamine levels. J Physiol. 1982 Feb;323:403–414. doi: 10.1113/jphysiol.1982.sp014080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carraway R., Kitabgi P., Leeman S. E. The amino acid sequence of radioimmunoassayable neurotensin from bovine intestine. J Biol Chem. 1978 Nov 25;253(22):7996–7998. [PubMed] [Google Scholar]
  9. Carraway R., Leeman S. E. The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J Biol Chem. 1973 Oct 10;248(19):6854–6861. [PubMed] [Google Scholar]
  10. Chahl L. A. The effect of putative peptide neurotransmitters on cutaneous vascular permeability in the rat. Naunyn Schmiedebergs Arch Pharmacol. 1979 Nov;309(2):159–163. doi: 10.1007/BF00501224. [DOI] [PubMed] [Google Scholar]
  11. Chahl L. A., Walker S. B. Responses of the rat cardiovascular system to substance P, neurotensin and bombesin. Life Sci. 1981 Nov 9;29(19):2009–2015. doi: 10.1016/0024-3205(81)90611-1. [DOI] [PubMed] [Google Scholar]
  12. Flavahan N. A., McGrath J. C. alpha 1-adrenoceptor activation can increase heart rate directly or decrease it indirectly through parasympathetic activation. Br J Pharmacol. 1982 Oct;77(2):319–328. doi: 10.1111/j.1476-5381.1982.tb09301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gardiner S. M., Bennett T., Compton A. M. Regional haemodynamic effects of neuropeptide Y, vasopressin and angiotensin II in conscious, unrestrained, Long Evans and Brattleboro rats. J Auton Nerv Syst. 1988 Sep;24(1-2):15–27. doi: 10.1016/0165-1838(88)90131-2. [DOI] [PubMed] [Google Scholar]
  14. Gardiner S. M., Bennett T. Regional hemodynamic responses to adrenoceptor antagonism in conscious rats. Am J Physiol. 1988 Oct;255(4 Pt 2):H813–H824. doi: 10.1152/ajpheart.1988.255.4.H813. [DOI] [PubMed] [Google Scholar]
  15. Gardiner S. M., Compton A. M., Bennett T. Effects of indomethacin on the regional haemodynamic responses to low doses of endothelins and sarafotoxin. Br J Pharmacol. 1990 May;100(1):158–162. doi: 10.1111/j.1476-5381.1990.tb12069.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gardiner S. M., Compton A. M., Bennett T., Palmer R. M., Moncada S. Control of regional blood flow by endothelium-derived nitric oxide. Hypertension. 1990 May;15(5):486–492. doi: 10.1161/01.hyp.15.5.486. [DOI] [PubMed] [Google Scholar]
  17. Gardiner S. M., Kemp P. A., Bennett T. Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats. Br J Pharmacol. 1991 Jul;103(3):1725–1732. doi: 10.1111/j.1476-5381.1991.tb09854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hammer R. A., Leeman S. E., Carraway R., Williams R. H. Isolation of human intestinal neurotensin. J Biol Chem. 1980 Mar 25;255(6):2476–2480. [PubMed] [Google Scholar]
  19. Haywood J. R., Shaffer R. A., Fastenow C., Fink G. D., Brody M. J. Regional blood flow measurement with pulsed Doppler flowmeter in conscious rat. Am J Physiol. 1981 Aug;241(2):H273–H278. doi: 10.1152/ajpheart.1981.241.2.H273. [DOI] [PubMed] [Google Scholar]
  20. Helke C. J., Eskay R. L. Capsaicin reduces substance P immunoreactivity in the lateral nucleus of the solitary tract and nodose ganglion. Peptides. 1985;6 (Suppl 1):121–126. doi: 10.1016/0196-9781(85)90020-8. [DOI] [PubMed] [Google Scholar]
  21. Holmes J. C., Schneider F. H. Pentobarbitone inhibition of catecholamine secretion. Br J Pharmacol. 1973 Oct;49(2):205–213. doi: 10.1111/j.1476-5381.1973.tb08366.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Janssen P. J., Gardiner S. M., Compton A. M., Bennett T. Mechanisms contributing to the differential haemodynamic effects of bombesin and cholecystokinin in conscious, Long Evans rats. Br J Pharmacol. 1991 Jan;102(1):123–134. doi: 10.1111/j.1476-5381.1991.tb12143.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kobayashi R. M., Brown M., Vale W. Regional distribution of neurotensin and somatostatin in rat brain. Brain Res. 1977 May 13;126(3):584–588. doi: 10.1016/0006-8993(77)90613-8. [DOI] [PubMed] [Google Scholar]
  24. Kérouac R., Rioux F., St-Pierre S. Mechanism of neurotensin-induced pressor effect and tachycardia in guinea pigs. Life Sci. 1981 Jun 1;28(22):2477–2487. doi: 10.1016/0024-3205(81)90589-0. [DOI] [PubMed] [Google Scholar]
  25. Kérouac R., St-Pierre S., Rioux F. Influence of various drugs on the variations of blood pressure, hematocrit and plasma histamine caused by neurotensin and compound 48/80 in rats. Neuropeptides. 1982 Dec;3(2):145–157. doi: 10.1016/0143-4179(82)90010-5. [DOI] [PubMed] [Google Scholar]
  26. Manberg P. J., Youngblood W. W., Nemeroff C. B., Rossor M. N., Iversen L. L., Prange A. J., Jr, Kizer J. S. Regional distribution of neurotensin in human brain. J Neurochem. 1982 Jun;38(6):1777–1780. doi: 10.1111/j.1471-4159.1982.tb06664.x. [DOI] [PubMed] [Google Scholar]
  27. Pernow J. Co-release and functional interactions of neuropeptide Y and noradrenaline in peripheral sympathetic vascular control. Acta Physiol Scand Suppl. 1988;568:1–56. [PubMed] [Google Scholar]
  28. Quirion R., Rioux F., Regoli D. Chronotropic and inotropic effects of neurotensin on spontaneously beating auricles. Can J Physiol Pharmacol. 1978 Aug;56(4):671–673. doi: 10.1139/y78-108. [DOI] [PubMed] [Google Scholar]
  29. Quirion R., Rioux F., Regoli D., St-Pierre S. Compound 48/80 inhibits neurotensin-induced hypotension in rats. Life Sci. 1980 Nov 17;27(20):1889–1895. doi: 10.1016/0024-3205(80)90435-x. [DOI] [PubMed] [Google Scholar]
  30. Quirion R., Rioux F., Regoli D., St-Pierre S. Neurotensin-induced coronary vessels constriction in perfused rat hearts. Eur J Pharmacol. 1979 Apr 15;55(2):221–223. doi: 10.1016/0014-2999(79)90398-4. [DOI] [PubMed] [Google Scholar]
  31. Rioux F., Bachelard H., Barabé J., St-Pierre S. The cardiovascular response to epicardial application of neurotensin in guinea pigs. Peptides. 1986 Nov-Dec;7(6):1087–1094. doi: 10.1016/0196-9781(86)90138-5. [DOI] [PubMed] [Google Scholar]
  32. Rioux F., Bachelard H., Bernoussi A., St-Pierre S. Capsaicin-sensitive structures as potential target sites for neurotensin and bradykinin in guinea pig atria. Peptides. 1988 Jul-Aug;9(4):883–892. doi: 10.1016/0196-9781(88)90137-4. [DOI] [PubMed] [Google Scholar]
  33. Rioux F., Lemieux M., Lebel M. Further observations on the mechanism of the cardiovascular reflexes caused by exposure of the peritoneum to neurotensin. Peptides. 1990 Jul-Aug;11(4):805–816. doi: 10.1016/0196-9781(90)90198-e. [DOI] [PubMed] [Google Scholar]
  34. Rioux F., Quirion R., Leblanc M. A., Regoli D., St-Pierre S. Possible interactions between neurotensin and prostaglandins in the isolated rat portal vein. Life Sci. 1980 Jul 21;27(3):259–267. doi: 10.1016/0024-3205(80)90146-0. [DOI] [PubMed] [Google Scholar]
  35. Shulkes A., Chick P., Wong H., Walsh J. H. A radioimmunoassay for neurotensin in human plasma. Clin Chim Acta. 1982 Oct 13;125(1):49–58. doi: 10.1016/0009-8981(82)90044-4. [DOI] [PubMed] [Google Scholar]
  36. Stene-Larsen G., Helle K. B. Inotropic and chronotropic effects of neurotensin in the rat atrium and of physalaemin in the auricles of R. esculenta. Comp Biochem Physiol C. 1979;64C(2):279–283. doi: 10.1016/0306-4492(79)90064-9. [DOI] [PubMed] [Google Scholar]
  37. Sumners C., Phillips M. I., Richards E. M. Central pressor action of neurotensin in conscious rats. Hypertension. 1982 Nov-Dec;4(6):888–893. doi: 10.1161/01.hyp.4.6.888. [DOI] [PubMed] [Google Scholar]
  38. Uhl G. R., Snyder S. H. Regional and subcellular distributions of brain neurotensin. Life Sci. 1976 Dec 15;19(12):1827–1832. doi: 10.1016/0024-3205(76)90114-4. [DOI] [PubMed] [Google Scholar]
  39. Winn M. J., Gardiner S. M., Bennett T. Functional involvement of vasopressin in the maintenance of systemic arterial blood pressures after phenoxybenzamine or phentolamine administration: studies in Long-Evans and Brattleboro rats. J Pharmacol Exp Ther. 1985 Nov;235(2):500–505. [PubMed] [Google Scholar]
  40. Wright C. E., Angus J. A., Korner P. I. Vascular amplifier properties in renovascular hypertension in conscious rabbits. Hindquarter responses to constrictor and dilator stimuli. Hypertension. 1987 Feb;9(2):122–131. doi: 10.1161/01.hyp.9.2.122. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES