Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 May;94(1):73–86. doi: 10.1111/j.1476-5381.1988.tb11501.x

Evidence for reduced beta-adrenoceptor coupling to adenylate cyclase in femoral arteries from spontaneously hypertensive rats.

M Asano 1, K Masuzawa 1, T Matsuda 1
PMCID: PMC1853937  PMID: 2456812

Abstract

1. Arterial relaxant responses via beta-adrenoceptors have been demonstrated to be decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To determine which process of the beta-adrenoceptor.adenylate cyclase (AC) system is involved in the decreased responsiveness to beta-adrenoceptor stimulation, relaxant responses to forskolin and dibutyryl cyclic AMP (db cyclic AMP) were compared strips of femoral and mesenteric arteries isolated from 13 week-old SHR and age-matched WKY. 2. The relaxant response to either forskolin, an activator of AC, or db cyclic AMP was not significantly different between the SHR and WKY, when the strips of both arteries from both strains were contracted with K+ to an equivalent magnitude (85% of the maximum). 3. Under the same conditions, however, the relaxant response to noradrenaline (NA) via beta-adrenoceptors was significantly decreased in the SHR arteries. 4. When the strips of femoral arteries were contracted with the same concentration of K+, there was a precontraction of greater magnitude in response to the K+ and a decreased relaxation in response to forskolin, db cyclic AMP or NA in the SHR. On the other hand, when the strips of mesenteric arteries were contracted with the same concentration of K+, the precontraction was smaller in magnitude and there was an increased relaxation in the SHR. 5. The relationship between the relaxant responses and the K+-induced precontractions clearly showed that the ability of forskolin and NA to relax the K+-contracted strips depends on the magnitude of precontraction. Therefore, a difference in magnitude of precontraction between the two groups may produce a meaningless difference. 6. The relaxant responses to forskolin and NA were significantly potentiated by the addition of isobutyl methylxanthine (IBMX), an inhibitor of cyclic AMP phosphodiesterase. Even in the presence of IBMX, relaxant responses to forskolin were the same for the two strains. The difference in the pD2 value for NA-induced relaxation between the two strains was the same in the presence and absence of IBMX. 7. The relaxant effect of either nitroprusside or nifedipine, agents which are independent of this system, was not significantly different between the strips from SHR and WKY. These relaxations were not potentiated by IBMX. 8. From these results, it is concluded that the reduced beta-adrenoceptor coupling to AC is mainly involved in the decreased responsiveness to beta-adrenoceptor stimulation. Furthermore, for an accurate comparison to be made, it is necessary to minimize the influence of variations in the magnitude of precontraction on the relaxant responses.

Full text

PDF
73

Selected References

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

  1. Amer M. S. Cyclic adenosine monophosphate and hypertension in rats. Science. 1973 Feb 23;179(4075):807–809. doi: 10.1126/science.179.4075.807. [DOI] [PubMed] [Google Scholar]
  2. Amer M. S., Gomoll A. W., Perhach J. L., Jr, Ferguson H. C., McKinney G. R. Aberrations of cyclic nucleotide metabolism in the hearts and vessels of hypertensive rats. Proc Natl Acad Sci U S A. 1974 Dec;71(12):4930–4934. doi: 10.1073/pnas.71.12.4930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Aoki K., Asano M. Effects of Bay K 8644 and nifedipine on femoral arteries of spontaneously hypertensive rats. Br J Pharmacol. 1986 May;88(1):221–230. doi: 10.1111/j.1476-5381.1986.tb09490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Asano M., Aoki K., Matsuda T. Contractile effects of Bay k 8644, a dihydropyridine calcium agonist, on isolated femoral arteries from spontaneously hypertensive rats. J Pharmacol Exp Ther. 1986 Oct;239(1):198–205. [PubMed] [Google Scholar]
  5. Asano M., Aoki K., Matsuda T. Reduced beta adrenoceptor interactions of norepinephrine enhance contraction in the femoral artery from spontaneously hypertensive rats. J Pharmacol Exp Ther. 1982 Oct;223(1):207–214. [PubMed] [Google Scholar]
  6. Asano M., Hidaka H. Pharmacological properties of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist in arterial strips from rats and rabbits. J Pharmacol Exp Ther. 1985 Aug;234(2):476–484. [PubMed] [Google Scholar]
  7. Bender J. L., Wolf L. G., Neer E. J. Interaction of forskolin with resolved adenylate cyclase components. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:101–109. [PubMed] [Google Scholar]
  8. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  9. Cohen M. L., Berkowitz B. A. Age-related changes in vascular responsiveness to cyclic nucleotides and contractile agonists. J Pharmacol Exp Ther. 1974 Oct;191(1):147–155. [PubMed] [Google Scholar]
  10. Cohen M. L., Berkowitz B. A. Decreased vascular relaxation in hypertension. J Pharmacol Exp Ther. 1976 Feb;196(2):396–406. [PubMed] [Google Scholar]
  11. Daly J. W. Forskolin, adenylate cyclase, and cell physiology: an overview. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:81–89. [PubMed] [Google Scholar]
  12. Donnelly T. E., Jr Lack of altered cyclic nucleotide phosphodiesterase activity in the aorta and heart of the spontaneously hypertensive rat. Biochim Biophys Acta. 1978 Aug 17;542(2):245–252. doi: 10.1016/0304-4165(78)90020-x. [DOI] [PubMed] [Google Scholar]
  13. Duckles S. P., Hurlbert J. S. Effect of age on beta adrenergic relaxation of the rat jugular vein. J Pharmacol Exp Ther. 1986 Jan;236(1):71–74. [PubMed] [Google Scholar]
  14. Fleisch J. H. Age-related changes in the sensitivity of blood vessels to drugs. Pharmacol Ther. 1980;8(2):477–487. doi: 10.1016/0163-7258(80)90055-8. [DOI] [PubMed] [Google Scholar]
  15. Fleisch J. H., Maling H. M., Brodie B. B. Beta-receptor activity in aorta; variations with age and species. Circ Res. 1970 Feb;26(2):151–162. doi: 10.1161/01.res.26.2.151. [DOI] [PubMed] [Google Scholar]
  16. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  17. Ramanathan S., Shibata S. Cyclic amp blood vessels of spontnaeously hypertensive rat. Blood Vessels. 1974;11(5-6):312–318. doi: 10.1159/000158024. [DOI] [PubMed] [Google Scholar]
  18. Seamon K. B., Daly J. W. Forskolin: a unique diterpene activator of cyclic AMP-generating systems. J Cyclic Nucleotide Res. 1981;7(4):201–224. [PubMed] [Google Scholar]
  19. Silver P. J., Michalak R. J., Kocmund S. M. Role of cyclic AMP protein kinase in decreased arterial cyclic AMP responsiveness in hypertension. J Pharmacol Exp Ther. 1985 Mar;232(3):595–601. [PubMed] [Google Scholar]
  20. Triner L., Vulliemoz Y., Verosky M., Manger W. M. Cyclic adenosine monophosphate and vascular reactivity in spontaneously hypertensive rats. Biochem Pharmacol. 1975 Mar 15;24(6):743–745. doi: 10.1016/0006-2952(75)90253-1. [DOI] [PubMed] [Google Scholar]
  21. Tsujimoto G., Lee C. H., Hoffman B. B. Age-related decrease in beta adrenergic receptor-mediated vascular smooth muscle relaxation. J Pharmacol Exp Ther. 1986 Nov;239(2):411–415. [PubMed] [Google Scholar]
  22. Vegesna R. V., Diamond J. Effects of isoproterenol and forskolin on tension, cyclic AMP levels, and cyclic AMP dependent protein kinase activity in bovine coronary artery. Can J Physiol Pharmacol. 1984 Sep;62(9):1116–1123. doi: 10.1139/y84-187. [DOI] [PubMed] [Google Scholar]

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

RESOURCES