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. 1991 Feb;102(2):478–482. doi: 10.1111/j.1476-5381.1991.tb12197.x

Diabetes-induced changes in cardiac beta-adrenoceptor responsiveness: effects of aldose reductase inhibition with ponalrestat.

C E Austin 1, R Chess-Williams 1
PMCID: PMC1918039  PMID: 1849772

Abstract

1. The responses of isolated left atria and papillary muscles to isoprenaline, forskolin and calcium have been examined in 3 week streptozotocin-diabetic rats and the effects of oral ponalrestat administration (25 mg kg-1 daily) on diabetes-induced changes in cardiac responsiveness investigated. 2. Three weeks after animals were made diabetic, cardiac responses to isoprenaline were enhanced and this was accompanied by an increase in the density of ventricular [3H]dihydroalprenolol binding sites. Treatment of animals with ponalrestat prevented the increase in cardiac beta-adrenoceptor responsiveness and receptor number. 3. Diabetes also enhanced the sensitivity of cardiac tissues to forskolin, an effect that was not prevented by the treatment of animals with ponalrestat. 4. Ponalrestat treatment increased the resting and maximum tensions developed by cardiac tissues from diabetic animals and increased the maximum tensions developed by tissues from control animals. Diabetes alone had no effect on resting or maximum developed tensions. 5. Ponalrestat therefore prevents the changes in beta-adrenoceptor density and responsiveness induced by short-term diabetes in the rat and also increases the tension developed by cardiac muscle, an effect observed in diabetic and normal animals.

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Selected References

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  1. Akiyama N., Okumura K., Watanabe Y., Hashimoto H., Ito T., Ogawa K., Satake T. Altered acetylcholine and norepinephrine concentrations in diabetic rat hearts. Role of parasympathetic nervous system in diabetic cardiomyopathy. Diabetes. 1989 Feb;38(2):231–236. doi: 10.2337/diab.38.2.231. [DOI] [PubMed] [Google Scholar]
  2. Bielefeld D. R., Pace C. S., Boshell B. R. Altered sensitivity of chronic diabetic rat heart to calcium. Am J Physiol. 1983 Dec;245(6):E560–E567. doi: 10.1152/ajpendo.1983.245.6.E560. [DOI] [PubMed] [Google Scholar]
  3. Cameron N. E., Cotter M. A., Robertson S. Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition. Diabetologia. 1989 Jun;32(6):365–370. doi: 10.1007/BF00277260. [DOI] [PubMed] [Google Scholar]
  4. Chess-Williams R. G., Broadley K. J., Sheridan D. J. Cardiac post-junctional alpha 1- and beta-adrenoceptors: effects of chronic chemical sympathectomy with 6-hydroxydopamine. J Recept Res. 1987;7(5):713–728. doi: 10.3109/10799898709056781. [DOI] [PubMed] [Google Scholar]
  5. Chess-Williams R. G., Grassby P. F., Broadley K. J., Sheridan D. J. Cardiac alpha- and beta-adrenoceptor sensitivity and binding characteristics after chronic reserpine pretreatment. Naunyn Schmiedebergs Arch Pharmacol. 1987 Dec;336(6):646–651. doi: 10.1007/BF00165755. [DOI] [PubMed] [Google Scholar]
  6. Clarke B. F., Ewing D. J., Campbell I. W. Diabetic autonomic neuropathy. Diabetologia. 1979 Oct;17(4):195–212. doi: 10.1007/BF01235856. [DOI] [PubMed] [Google Scholar]
  7. Daly J. W. Forskolin, adenylate cyclase, and cell physiology: an overview. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:81–89. [PubMed] [Google Scholar]
  8. Fukushi S., Merola L. O., Kinoshita J. H. Altering the course of cataracts in diabetic rats. Invest Ophthalmol Vis Sci. 1980 Mar;19(3):313–315. [PubMed] [Google Scholar]
  9. Ganguly P. K., Pierce G. N., Dhalla K. S., Dhalla N. S. Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol. 1983 Jun;244(6):E528–E535. doi: 10.1152/ajpendo.1983.244.6.E528. [DOI] [PubMed] [Google Scholar]
  10. Goldfarb S., Simmons D. A., Kern E. F. Amelioration of glomerular hyperfiltration in acute experimental diabetes mellitus by dietary myo-inositol supplementation and aldose reductase inhibition. Trans Assoc Am Physicians. 1986;99:67–72. [PubMed] [Google Scholar]
  11. Harati Y. Diabetic peripheral neuropathies. Ann Intern Med. 1987 Oct;107(4):546–559. doi: 10.7326/0003-4819-107-4-546. [DOI] [PubMed] [Google Scholar]
  12. Hawthorn M. H., Chess-Williams R. G., Grassby P. F., Broadley K. J. The use of forskolin to investigate the site of cardiac beta-adrenoreceptor supersensitivity. J Auton Pharmacol. 1985 Sep;5(3):231–239. doi: 10.1111/j.1474-8673.1985.tb00124.x. [DOI] [PubMed] [Google Scholar]
  13. Heyliger C. E., Prakash A., McNeill J. H. Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus. Am J Physiol. 1987 Mar;252(3 Pt 2):H540–H544. doi: 10.1152/ajpheart.1987.252.3.H540. [DOI] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Laurenza A., Sutkowski E. M., Seamon K. B. Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action? Trends Pharmacol Sci. 1989 Nov;10(11):442–447. doi: 10.1016/S0165-6147(89)80008-2. [DOI] [PubMed] [Google Scholar]
  16. Rodger I. W., Shahid M. Forskolin, cyclic nucleotides and positive inotropism in isolated papillary muscles of the rabbit. Br J Pharmacol. 1984 Jan;81(1):151–159. doi: 10.1111/j.1476-5381.1984.tb10755.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Schimmel R. J. Stimulation of cAMP accumulation and lipolysis in hamster adipocytes with forskolin. Am J Physiol. 1984 Jan;246(1 Pt 1):C63–C68. doi: 10.1152/ajpcell.1984.246.1.C63. [DOI] [PubMed] [Google Scholar]
  18. Stribling D., Mirrlees D. J., Harrison H. E., Earl D. C. Properties of ICI 128,436, a novel aldose reductase inhibitor, and its effects on diabetic complications in the rat. Metabolism. 1985 Apr;34(4):336–344. doi: 10.1016/0026-0495(85)90223-9. [DOI] [PubMed] [Google Scholar]
  19. Tomlinson D. R., Moriarty R. J., Mayer J. H. Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil. Diabetes. 1984 May;33(5):470–476. doi: 10.2337/diab.33.5.470. [DOI] [PubMed] [Google Scholar]
  20. Yoshida T., Nishioka H., Nakamura Y., Kondo M. Reduced noradrenaline turnover in streptozotocin-induced diabetic rats. Diabetologia. 1985 Sep;28(9):692–696. doi: 10.1007/BF00291978. [DOI] [PubMed] [Google Scholar]
  21. Yoshida T., Nishioka H., Yoshioka K., Nakano K., Kondo M., Terashima H. Effect of aldose reductase inhibitor ONO 2235 on reduced sympathetic nervous system activity and peripheral nerve disorders in STZ-induced diabetic rats. Diabetes. 1987 Jan;36(1):6–13. doi: 10.2337/diab.36.1.6. [DOI] [PubMed] [Google Scholar]

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