Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1992 Jan;33(1):83–87. doi: 10.1111/j.1365-2125.1992.tb04004.x

Age-related changes in adenosine and beta-adrenoceptor responsiveness of vascular smooth muscle in man.

G A Ford 1, B B Hoffman 1, R E Vestal 1, T F Blaschke 1
PMCID: PMC1381203  PMID: 1311596

Abstract

1. Ageing is associated with a decline in beta-adrenergic responsiveness in several tissues. Reduced beta-adrenoceptor mediated smooth muscle relaxation in aged man has been demonstrated using the dorsal hand vein technique. Isoprenaline and adenosine activate adenylate cyclase through separate membrane bound receptors to induce vasodilatation. 2. To determine the specificity of reduced beta-adrenergic responsiveness in smooth muscle of aged man, and possible sites of the defect responsible, venodilatory responses to isoprenaline, a beta-adrenoceptor agonist and adenosine were determined in nine young (age 26 +/- 3 years: mean +/- s.d.) and eight elderly (age 70 +/- 5 years), healthy male volunteers. Veins were partially constricted with the alpha 1-adrenoceptor agonist phenylephrine and increasing doses of adenosine (5 to 1220 micrograms min-1) or isoprenaline (271 ng min-1) were infused. 3. Maximal dilatation induced by isoprenaline was 83 +/- 26% in the young and 51 +/- 34% in the elderly, P = 0.02. Maximal dilatation induced at the highest dose of adenosine (1220 micrograms min-1) was similar in young and elderly: 79 +/- 25% vs 88 +/- 28%, P = 0.26. 4. Adenosine venodilatation was measured before and after infusions of theophylline (6.8 to 135 micrograms min-1) for 30 min in six subjects. Adenosine responsiveness was unchanged following theophylline: 48 +/- 16% to 49 +/- 40%, P = 0.44. 5. The results suggest that the age-associated reduced responsiveness of the beta-adrenergic system in human vascular smooth muscle is not shared by venodilatation mediated by adenosine.

Full text

PDF
83

Selected References

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

  1. Abrass I. B., Scarpace P. J. Human lymphocyte beta-adrenergic receptors are unaltered with age. J Gerontol. 1981 May;36(3):298–301. doi: 10.1093/geronj/36.3.298. [DOI] [PubMed] [Google Scholar]
  2. Chin J. H., Hoffman B. B. Age-related deficit in beta receptor stimulation of cAMP binding in blood vessels. Mech Ageing Dev. 1990 Apr 9;53(2):111–125. doi: 10.1016/0047-6374(90)90064-m. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. De Mey J. G., Vanhoutte P. M. Role of the intima in cholinergic and purinergic relaxation of isolated canine femoral arteries. J Physiol. 1981 Jul;316:347–355. doi: 10.1113/jphysiol.1981.sp013792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Deisher T. A., Mankani S., Hoffman B. B. Role of cyclic AMP-dependent protein kinase in the diminished beta adrenergic responsiveness of vascular smooth muscle with increasing age. J Pharmacol Exp Ther. 1989 Jun;249(3):812–819. [PubMed] [Google Scholar]
  6. Doyle V., O'Malley K., Kelly J. G. Human lymphocyte beta-adrenoceptor density in relation to age and hypertension. J Cardiovasc Pharmacol. 1982 Sep-Oct;4(5):738–740. doi: 10.1097/00005344-198209000-00007. [DOI] [PubMed] [Google Scholar]
  7. Eichler H. G., Hiremath A., Katzir D., Blaschke T. F., Hoffman B. B. Absence of age-related changes in venous responsiveness to nitroglycerin in vivo in humans. Clin Pharmacol Ther. 1987 Nov;42(5):521–524. doi: 10.1038/clpt.1987.191. [DOI] [PubMed] [Google Scholar]
  8. Ericsson E., Lundholm L. Adrenergic beta-receptor activity and cyclic AMP metabolism in vascular smooth muscle; variations with age. Mech Ageing Dev. 1975 Jan-Feb;4(1):1–6. doi: 10.1016/0047-6374(75)90002-0. [DOI] [PubMed] [Google Scholar]
  9. Feldman R. D., Limbird L. E., Nadeau J., Robertson D., Wood A. J. Alterations in leukocyte beta-receptor affinity with aging. A potential explanation for altered beta-adrenergic sensitivity in the elderly. N Engl J Med. 1984 Mar 29;310(13):815–819. doi: 10.1056/NEJM198403293101303. [DOI] [PubMed] [Google Scholar]
  10. Fredholm B. B., Sollevi A. Cardiovascular effects of adenosine. Clin Physiol. 1986 Feb;6(1):1–21. doi: 10.1111/j.1475-097x.1986.tb00139.x. [DOI] [PubMed] [Google Scholar]
  11. Hayashi S., Toda N. Age-related changes in the response of rabbit isolated aortae to vasoactive agents. Br J Pharmacol. 1978 Oct;64(2):229–237. doi: 10.1111/j.1476-5381.1978.tb17294.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hiremath A. N., Pershe R. A., Hoffman B. B., Blaschke T. F. Comparison of age-related changes in prostaglandin E1 and beta-adrenergic responsiveness of vascular smooth muscle in adult males. J Gerontol. 1989 Jan;44(1):M13–M17. doi: 10.1093/geronj/44.1.m13. [DOI] [PubMed] [Google Scholar]
  13. Hoffman B. B., Chang H., Farahbakhsh Z., Reaven G. Inhibition of lipolysis by adenosine is potentiated with age. J Clin Invest. 1984 Nov;74(5):1750–1755. doi: 10.1172/JCI111593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kalaria R. N., Andorn A. C., Tabaton M., Whitehouse P. J., Harik S. I., Unnerstall J. R. Adrenergic receptors in aging and Alzheimer's disease: increased beta 2-receptors in prefrontal cortex and hippocampus. J Neurochem. 1989 Dec;53(6):1772–1781. doi: 10.1111/j.1471-4159.1989.tb09242.x. [DOI] [PubMed] [Google Scholar]
  15. Krall J. F., Connelly-Fittingoff M., Tuck M. L. Lymphocyte adenylate cyclase and human aging. Proc Soc Exp Biol Med. 1983 Sep;173(4):475–480. doi: 10.3181/00379727-173-41673. [DOI] [PubMed] [Google Scholar]
  16. McCormack D. G., Clarke B., Barnes P. J. Characterization of adenosine receptors in human pulmonary arteries. Am J Physiol. 1989 Jan;256(1 Pt 2):H41–H46. doi: 10.1152/ajpheart.1989.256.1.H41. [DOI] [PubMed] [Google Scholar]
  17. Pan H. Y., Hoffman B. B., Pershe R. A., Blaschke T. F. Decline in beta adrenergic receptor-mediated vascular relaxation with aging in man. J Pharmacol Exp Ther. 1986 Dec;239(3):802–807. [PubMed] [Google Scholar]
  18. Robinson B. F. Assessment of the effect of drugs on the venous system in man. Br J Clin Pharmacol. 1978 Nov;6(5):381–386. doi: 10.1111/j.1365-2125.1978.tb04600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Scarpace P. J., Tumer N., Mader S. L. Beta-adrenergic function in aging. Basic mechanisms and clinical implications. Drugs Aging. 1991 Mar;1(2):116–129. doi: 10.2165/00002512-199101020-00004. [DOI] [PubMed] [Google Scholar]
  20. Schoeffter P., Stoclet J. C. Age-related decrease of in vitro isoproterenol-induced cyclic AMP accumulation in rat aorta. Eur J Pharmacol. 1982 Jan 22;77(2-3):183–186. doi: 10.1016/0014-2999(82)90017-6. [DOI] [PubMed] [Google Scholar]
  21. Sollevi A. Cardiovascular effects of adenosine in man; possible clinical implications. Prog Neurobiol. 1986;27(4):319–349. doi: 10.1016/0301-0082(86)90005-5. [DOI] [PubMed] [Google Scholar]
  22. Toda N., Okunishi H., Taniyama K., Miyazaki M. Responses to adenine nucleotides and related compounds of isolated dog cerebral, coronary and mesenteric arteries. Blood Vessels. 1982;19(5):226–236. doi: 10.1159/000158389. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Vanhoutte P. M., Collis M. G., Janssens W. J., Verbeuren T. J. Calcium dependence of prejunctional inhibitory effects of adenosine and acetylcholine on adrenergic neurotransmission in canine saphenous veins. Eur J Pharmacol. 1981 Jun 19;72(2-3):189–198. doi: 10.1016/0014-2999(81)90273-9. [DOI] [PubMed] [Google Scholar]
  25. Verhaeghe R. H. Action of adenosine and adenine nucleotides on dogs' isolated veins. Am J Physiol. 1977 Jul;233(1):H114–H121. doi: 10.1152/ajpheart.1977.233.1.H114. [DOI] [PubMed] [Google Scholar]
  26. Vestal R. E., Wood A. J., Shand D. G. Reduced beta-adrenoceptor sensitivity in the elderly. Clin Pharmacol Ther. 1979 Aug;26(2):181–186. doi: 10.1002/cpt1979262181. [DOI] [PubMed] [Google Scholar]
  27. Volicer L., West C. D., Chase A. R., Greene L. beta-adrenergic receptor sensitivity in cultured vascular smooth muscle cells: effect of age and of dietary restriction. Mech Ageing Dev. 1983 Mar-Apr;21(3-4):283–293. doi: 10.1016/0047-6374(83)90047-7. [DOI] [PubMed] [Google Scholar]
  28. Watt A. H., Bayer A., Routledge P. A., Swift C. G. Adenosine-induced respiratory and heart rate changes in young and elderly adults. Br J Clin Pharmacol. 1989 Feb;27(2):265–267. doi: 10.1111/j.1365-2125.1989.tb05360.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Yen M. H., Wu C. C., Chiou W. F. Partially endothelium-dependent vasodilator effect of adenosine in rat aorta. Hypertension. 1988 Jun;11(6 Pt 1):514–518. doi: 10.1161/01.hyp.11.6.514. [DOI] [PubMed] [Google Scholar]
  30. van Brummelen P., Bühler F. R., Kiowski W., Amann F. W. Age-related decrease in cardiac and peripheral vascular responsiveness to isoprenaline: studies in normal subjects. Clin Sci (Lond) 1981 May;60(5):571–577. doi: 10.1042/cs0600571. [DOI] [PubMed] [Google Scholar]

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

RESOURCES