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. 1991 Jun;103(2):1509–1514. doi: 10.1111/j.1476-5381.1991.tb09818.x

Regional haemodynamic effects of prolonged infusions of human alpha-calcitonin gene-related peptide in conscious, Long Evans rats.

S M Gardiner 1, A M Compton 1, P A Kemp 1, T Bennett 1, R Foulkes 1, B Hughes 1
PMCID: PMC1908353  PMID: 1884105

Abstract

1. Haemodynamic measurements were made in conscious, Long Evans rats chronically instrumented for the assessment of changes in regional blood flows (renal, mesenteric and hindquarters, or internal and common carotid) and systemic arterial blood pressure and heart rate, before, during and after 3 day infusions of vehicle or human alpha-calcitonin gene-related peptide (CGRP) (1.5 or 15 nmol kg-1 h-1). 2. In animals with renal, mesenteric and hindquarters flow probes (n = 8), during the first day of infusion of human alpha-CGRP (1.5 nmol kg-1 h-1) there was sustained tachycardia and hypotension, a sustained reduction in renal flow, a transient reduction in mesenteric flow and a relatively well-maintained increase in hindquarters flow. All these effects were significantly different from the changes seen in vehicle-infused rats (n = 8), but calculation of vascular conductances showed only the late mesenteric vasodilatation and the sustained hindquarters vasodilatation were different from the changes in vehicle-infused rats. However, by the second day of infusion and thereafter cardiovascular variables in the animals receiving vehicle and those receiving human alpha-CGRP were not different. 3. Nine animals instrumented with probes to monitor changes in internal and common carotid haemodynamics initially received human alpha-CGRP infused at a rate of 1.5 nmol kg-1 h-1. Three of these animals still showed some response to the human alpha-CGRP (tachycardia, hypotension, hyperaemic vasodilatation) throughout the second day of infusion and hence were taken through the 3 day infusion protocol. When the infusion was stopped on the fourth day all these animals showed reversal of the effects of human alpha-CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Brown Z. W., Amit Z., Weeks J. R. Simple flow-thru swivel for infusions into unrestrained animals. Pharmacol Biochem Behav. 1976 Sep;5(3):363–365. doi: 10.1016/0091-3057(76)90090-3. [DOI] [PubMed] [Google Scholar]
  2. Chakder S., Rattan S. [Tyr0]-calcitonin gene-related peptide 28-37 (rat) as a putative antagonist of calcitonin gene-related peptide responses on opossum internal anal sphincter smooth muscle. J Pharmacol Exp Ther. 1990 Apr;253(1):200–206. [PubMed] [Google Scholar]
  3. Dennis T., Fournier A., St Pierre S., Quirion R. Structure-activity profile of calcitonin gene-related peptide in peripheral and brain tissues. Evidence for receptor multiplicity. J Pharmacol Exp Ther. 1989 Nov;251(2):718–725. [PubMed] [Google Scholar]
  4. Gardiner S. M., Compton A. M., Bennett T., Kemp P. A., Ney U. Synergistic internal carotid vasodilator effects of human alpha-calcitonin gene-related peptide and nimodipine in conscious rats. Br J Pharmacol. 1990 Apr;99(4):830–834. doi: 10.1111/j.1476-5381.1990.tb13015.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gardiner S. M., Compton A. M., Bennett T. Regional haemodynamic effects of human alpha- and beta-calcitonin gene-related peptide in conscious Wistar rats. Br J Pharmacol. 1989 Dec;98(4):1225–1232. doi: 10.1111/j.1476-5381.1989.tb12668.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gardiner S. M., Compton A. M., Bennett T. Regional hemodynamic effects of calcitonin gene-related peptide. Am J Physiol. 1989 Feb;256(2 Pt 2):R332–R338. doi: 10.1152/ajpregu.1989.256.2.R332. [DOI] [PubMed] [Google Scholar]
  7. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T., Bose C., Foulkes R., Hughes B. Antagonistic effect of human alpha-CGRP [8-37] on the in vivo regional haemodynamic actions of human alpha-CGRP. Biochem Biophys Res Commun. 1990 Sep 28;171(3):938–943. doi: 10.1016/0006-291x(90)90774-h. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T. Regional and cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats. Br J Pharmacol. 1990 Nov;101(3):625–631. doi: 10.1111/j.1476-5381.1990.tb14131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Han S. P., Naes L., Westfall T. C. Inhibition of periarterial nerve stimulation-induced vasodilation of the mesenteric arterial bed by CGRP (8-37) and CGRP receptor desensitization. Biochem Biophys Res Commun. 1990 Apr 30;168(2):786–791. doi: 10.1016/0006-291x(90)92390-l. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Johnston F. G., Bell B. A., Robertson I. J., Miller J. D., Haliburn C., O'Shaughnessy D., Riddell A. J., O'Laoire S. A. Effect of calcitonin-gene-related peptide on postoperative neurological deficits after subarachnoid haemorrhage. Lancet. 1990 Apr 14;335(8694):869–872. doi: 10.1016/0140-6736(90)90473-i. [DOI] [PubMed] [Google Scholar]
  12. Le Grevès P., Nyberg F., Hökfelt T., Terenius L. Calcitonin gene-related peptide is metabolized by an endopeptidase hydrolyzing substance P. Regul Pept. 1989 Jun-Jul;25(3):277–286. doi: 10.1016/0167-0115(89)90176-6. [DOI] [PubMed] [Google Scholar]
  13. Maton P. N., Pradhan T., Zhou Z. C., Gardner J. D., Jensen R. T. Activities of calcitonin gene-related peptide (CGRP) and related peptides at the CGRP receptor. Peptides. 1990 May-Jun;11(3):485–489. doi: 10.1016/0196-9781(90)90047-9. [DOI] [PubMed] [Google Scholar]
  14. Sirén A. L., Feuerstein G. Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat. J Pharmacol Exp Ther. 1988 Oct;247(1):69–78. [PubMed] [Google Scholar]
  15. Takata Y., Hutchinson J. S. Exaggerated hypotensive responses to calcium antagonists in spontaneously hypertensive rats. Clin Exp Hypertens A. 1983;5(6):827–847. doi: 10.3109/10641968309081811. [DOI] [PubMed] [Google Scholar]
  16. Theodorsson-Norheim E. Friedman and Quade tests: BASIC computer program to perform nonparametric two-way analysis of variance and multiple comparisons on ranks of several related samples. Comput Biol Med. 1987;17(2):85–99. doi: 10.1016/0010-4825(87)90003-5. [DOI] [PubMed] [Google Scholar]
  17. Thoren P., Noresson E., Ricksten S. E. Cardiac reflexes in normotensive and spontaneously hypertensive rats. Am J Cardiol. 1979 Oct 22;44(5):884–888. doi: 10.1016/0002-9149(79)90218-2. [DOI] [PubMed] [Google Scholar]
  18. Unger T., Demmert G., Rohmeiss P., Veelken R., Luft F. C. Dissociation between heart rate and sympathetic nerve responses to baroreceptor activation in spontaneously hypertensive rats. J Cardiovasc Pharmacol. 1987;10 (Suppl 12):S221–S224. [PubMed] [Google Scholar]
  19. Verberne A. J., Young N. A., Louis W. J. Impairment of inhibitory cardiopulmonary vagal reflexes in spontaneously hypertensive rats. J Auton Nerv Syst. 1988 Jun;23(1):63–68. doi: 10.1016/0165-1838(88)90167-1. [DOI] [PubMed] [Google Scholar]

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