Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Sep;110(1):404–410. doi: 10.1111/j.1476-5381.1993.tb13824.x

Nitric oxide-dependent and -independent hyperaemia due to calcitonin gene-related peptide in the rat stomach.

P Holzer 1, I T Lippe 1, M Jocic 1, C Wachter 1, R Erb 1, A Heinemann 1
PMCID: PMC2175986  PMID: 8220901

Abstract

1. Calcitonin gene-related peptide (CGRP) potently enhances mucosal blood flow in the rat stomach. The aim of this study was to examine whether CGRP also dilates extramural arteries supplying the stomach and whether the vasodilator action of CGRP involves nitric oxide (NO). 2. Rat CGRP-alpha (0.03-1 nmol kg-1, i.v.) produced a dose-dependent increase in blood flow through the left gastric artery (LGA) as determined by an ultrasonic transit time technique in urethane-anaesthetized rats. Blockade of NO synthesis by NG-nitro-L-arginine methyl ester (L-NAME, 20 and 60 mumol kg-1, i.v.) significantly reduced basal blood flow (BF) in the LGA and attenuated the hyperaemic activity of CGRP by a factor of 2.8-4. D-NAME tended to enhance basal BF in the LGA but had no influence on the dilator activity of CGRP. The ability of vasoactive intestinal polypeptide to increase left gastric arterial blood flow remained unaltered by L-NAME. 3. L-NAME (20 and 60 mumol kg-1, i.v.) evoked a prompt and sustained rise of mean arterial blood pressure (MAP) and caused a slight decrease in the hypotensive activity of CGRP. In contrast, D-NAME induced a delayed and moderate increase in MAP and did not influence the hypotensive activity of CGRP. 4. Rat CGRP-alpha dilated the isolated perfused bed of the rat LGA precontracted with methoxamine and was 3 times more potent in this respect than rat CGRP-beta. The dilator action of rat CGRP-alpha in this preparation was not affected by L-NAME or D-NAME (40 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
404

Selected References

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

  1. Abdelrahman A., Wang Y. X., Chang S. D., Pang C. C. Mechanism of the vasodilator action of calcitonin gene-related peptide in conscious rats. Br J Pharmacol. 1992 May;106(1):45–48. doi: 10.1111/j.1476-5381.1992.tb14290.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauerfeind P., Hof R., Hof A., Cucala M., Siegrist S., von Ritter C., Fischer J. A., Blum A. L. Effects of hCGRP I and II on gastric blood flow and acid secretion in anesthetized rabbits. Am J Physiol. 1989 Jan;256(1 Pt 1):G145–G149. doi: 10.1152/ajpgi.1989.256.1.G145. [DOI] [PubMed] [Google Scholar]
  3. Bråtveit M., Haugan A., Helle K. B. Effects of calcitonin gene-related peptide (CGRP) on regional haemodynamics and on selected hepato-splanchnic arteries from the rat: a comparison with VIP and atriopeptin II. Scand J Clin Lab Invest. 1991 Apr;51(2):167–174. doi: 10.1080/00365519109091104. [DOI] [PubMed] [Google Scholar]
  4. Burnstock G. Local mechanisms of blood flow control by perivascular nerves and endothelium. J Hypertens Suppl. 1990 Dec;8(7):S95–106. [PubMed] [Google Scholar]
  5. Chen R. Y., Li D. S., Guth P. H. Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilation. Am J Physiol. 1992 May;262(5 Pt 2):H1350–H1355. doi: 10.1152/ajpheart.1992.262.5.H1350. [DOI] [PubMed] [Google Scholar]
  6. Della N. G., Papka R. E., Furness J. B., Costa M. Vasoactive intestinal peptide-like immunoreactivity in nerves associated with the cardiovascular system of guinea-pigs. Neuroscience. 1983 Jul;9(3):605–619. doi: 10.1016/0306-4522(83)90177-x. [DOI] [PubMed] [Google Scholar]
  7. Diez Guerra F. J., Zaidi M., Bevis P., MacIntyre I., Emson P. C. Evidence for release of calcitonin gene-related peptide and neurokinin A from sensory nerve endings in vivo. Neuroscience. 1988 Jun;25(3):839–846. doi: 10.1016/0306-4522(88)90039-5. [DOI] [PubMed] [Google Scholar]
  8. Gardiner S. M., Compton A. M., Kemp P. A., Bennett T., Foulkes R., Hughes B. Haemodynamic effects of human alpha-calcitonin gene-related peptide following administration of endothelin-1 or NG-nitro-L-arginine methyl ester in conscious rats. Br J Pharmacol. 1991 May;103(1):1256–1262. doi: 10.1111/j.1476-5381.1991.tb12333.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Gray D. W., Marshall I. Human alpha-calcitonin gene-related peptide stimulates adenylate cyclase and guanylate cyclase and relaxes rat thoracic aorta by releasing nitric oxide. Br J Pharmacol. 1992 Nov;107(3):691–696. doi: 10.1111/j.1476-5381.1992.tb14508.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Green T., Dockray G. J. Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea-pig. Neuroscience. 1988 Apr;25(1):181–193. doi: 10.1016/0306-4522(88)90017-6. [DOI] [PubMed] [Google Scholar]
  12. Holzer P., Guth P. H. Neuropeptide control of rat gastric mucosal blood flow. Increase by calcitonin gene-related peptide and vasoactive intestinal polypeptide, but not substance P and neurokinin A. Circ Res. 1991 Jan;68(1):100–105. doi: 10.1161/01.res.68.1.100. [DOI] [PubMed] [Google Scholar]
  13. Holzer P., Livingston E. H., Saria A., Guth P. H. Sensory neurons mediate protective vasodilatation in rat gastric mucosa. Am J Physiol. 1991 Mar;260(3 Pt 1):G363–G370. doi: 10.1152/ajpgi.1991.260.3.G363. [DOI] [PubMed] [Google Scholar]
  14. Holzer P., Peskar B. M., Peskar B. A., Amann R. Release of calcitonin gene-related peptide induced by capsaicin in the vascularly perfused rat stomach. Neurosci Lett. 1990 Jan 1;108(1-2):195–200. doi: 10.1016/0304-3940(90)90730-w. [DOI] [PubMed] [Google Scholar]
  15. Kawasaki H., Nuki C., Saito A., Takasaki K. Role of calcitonin gene-related peptide-containing nerves in the vascular adrenergic neurotransmission. J Pharmacol Exp Ther. 1990 Jan;252(1):403–409. [PubMed] [Google Scholar]
  16. Kwok Y. N., McIntosh C. H., Sy H., Brown J. C. Inhibitory actions of tachykinins and neurokinins on release of somatostatin-like immunoreactivity from the isolated perfused rat stomach. J Pharmacol Exp Ther. 1988 Aug;246(2):726–731. [PubMed] [Google Scholar]
  17. Li D. S., Raybould H. E., Quintero E., Guth P. H. Role of calcitonin gene-related peptide in gastric hyperemic response to intragastric capsaicin. Am J Physiol. 1991 Oct;261(4 Pt 1):G657–G661. doi: 10.1152/ajpgi.1991.261.4.G657. [DOI] [PubMed] [Google Scholar]
  18. Lippe I. T., Holzer P. Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back-diffusion. Br J Pharmacol. 1992 Mar;105(3):708–714. doi: 10.1111/j.1476-5381.1992.tb09043.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lippe I. T., Lorbach M., Holzer P. Close arterial infusion of calcitonin gene-related peptide into the rat stomach inhibits aspirin- and ethanol-induced hemorrhagic damage. Regul Pept. 1989 Aug;26(1):35–46. doi: 10.1016/0167-0115(89)90102-x. [DOI] [PubMed] [Google Scholar]
  20. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  21. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mulderry P. K., Ghatei M. A., Spokes R. A., Jones P. M., Pierson A. M., Hamid Q. A., Kanse S., Amara S. G., Burrin J. M., Legon S. Differential expression of alpha-CGRP and beta-CGRP by primary sensory neurons and enteric autonomic neurons of the rat. Neuroscience. 1988 Apr;25(1):195–205. doi: 10.1016/0306-4522(88)90018-8. [DOI] [PubMed] [Google Scholar]
  23. Peskar B. M., Respondek M., Müller K. M., Peskar B. A. A role for nitric oxide in capsaicin-induced gastroprotection. Eur J Pharmacol. 1991 May 30;198(1):113–114. doi: 10.1016/0014-2999(91)90572-8. [DOI] [PubMed] [Google Scholar]
  24. Pique J. M., Esplugues J. V., Whittle B. J. Endogenous nitric oxide as a mediator of gastric mucosal vasodilatation during acid secretion. Gastroenterology. 1992 Jan;102(1):168–174. doi: 10.1016/0016-5085(92)91797-8. [DOI] [PubMed] [Google Scholar]
  25. Rees D. D., Palmer R. M., Schulz R., Hodson H. F., Moncada S. Characterization of three inhibitors of endothelial nitric oxide synthase in vitro and in vivo. Br J Pharmacol. 1990 Nov;101(3):746–752. doi: 10.1111/j.1476-5381.1990.tb14151.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sternini C., Anderson K. Calcitonin gene-related peptide-containing neurons supplying the rat digestive system: differential distribution and expression pattern. Somatosens Mot Res. 1992;9(1):45–59. doi: 10.3109/08990229209144762. [DOI] [PubMed] [Google Scholar]
  27. Tepperman B. L., Whittle B. J. Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation. Br J Pharmacol. 1992 Jan;105(1):171–175. doi: 10.1111/j.1476-5381.1992.tb14230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Walder C. E., Thiemermann C., Vane J. R. Endothelium-derived relaxing factor participates in the increased blood flow in response to pentagastrin in the rat stomach mucosa. Proc Biol Sci. 1990 Sep 22;241(1302):195–200. doi: 10.1098/rspb.1990.0085. [DOI] [PubMed] [Google Scholar]
  29. Wang B. C., Bie P., Leadley R. J., Jr, Goetz K. L. Cardiovascular effects of calcitonin gene-related peptide in conscious dogs. Am J Physiol. 1989 Oct;257(4 Pt 2):R726–R731. doi: 10.1152/ajpregu.1989.257.4.R726. [DOI] [PubMed] [Google Scholar]
  30. Whittle B. J., Lopez-Belmonte J., Moncada S. Nitric oxide mediates rat mucosal vasodilatation induced by intragastric capsaicin. Eur J Pharmacol. 1992 Aug 6;218(2-3):339–341. doi: 10.1016/0014-2999(92)90188-a. [DOI] [PubMed] [Google Scholar]

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

RESOURCES