Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Aug;109(4):980–986. doi: 10.1111/j.1476-5381.1993.tb13717.x

Vasoreactivity and prostacyclin release in streptozotocin-diabetic rats: effects of insulin or aldose reductase inhibition.

E J Stevens 1, G B Willars 1, P Lidbury 1, F House 1, D R Tomlinson 1
PMCID: PMC2175753  PMID: 8401951

Abstract

1. Alterations in vasoreactivity and endothelial cell function could underlie some of the vascular abnormalities in diabetes. To examine aspects of these phenomena we studied the effects of 4-6 weeks streptozotocin-induced diabetes in the rat on basal and angiotensin II (AII)-stimulated prostacyclin release from isolated lung, perfused at constant flow. In addition, pressure was monitored throughout the lung perfusion as an index of vasomotor tone. 2. The experiment also included lungs from groups of diabetic rats treated with either insulin or an aldose reductase inhibitor (imirestat), to determine whether these treatments influenced the development of any defects seen in untreated diabetes. 3. Despite some indication of a trend towards reduced prostacyclin release in lungs from diabetic rats, neither the basal nor AII-stimulated release was significantly different from that seen in tissues from control animals. There were no significant differences between groups in the average basal perfusion pressure and in either the absolute pressure response to AII or the time of this peak. 4. The area under the perfusion pressure curve during AII infusion was greater in lungs from diabetic animals than in controls indicating a prolonged vasoconstrictor response. This increased pressor response may indicate increased sensitivity of diabetic tissue to AII or a reduced production of vasodilators in response to the vasoconstriction. 5. Whichever mechanism was responsible, this alteration was prevented by insulin treatment but not by aldose reductase inhibition, implicating mechanisms probably unrelated to exaggerated polyol pathway flux.

Full text

PDF
980

Selected References

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

  1. Abebe W., MacLeod K. M. Enhanced arterial contractility to noradrenaline in diabetic rats is associated with increased phosphoinositide metabolism. Can J Physiol Pharmacol. 1991 Mar;69(3):355–361. doi: 10.1139/y91-054. [DOI] [PubMed] [Google Scholar]
  2. Carreras L. O., Chamone D. A., Klerckx P., Vermylen J. Decreased vascular prostacyclin (PGI2) in diabetic rats. Stimulation of PGI2 release in normal and diabetic rats by the antithrombotic compound Bay g 6575. 1980 Aug 15-Sep 1Thromb Res. 19(4-5):663–670. doi: 10.1016/0049-3848(80)90038-9. [DOI] [PubMed] [Google Scholar]
  3. Craven P. A., DeRubertis F. R. Sorbinil suppresses glomerular prostaglandin production in the streptozotocin diabetic rat. Metabolism. 1989 Jul;38(7):649–654. doi: 10.1016/0026-0495(89)90102-9. [DOI] [PubMed] [Google Scholar]
  4. Durante W., Sen A. K., Sunahara F. A. Impairment of endothelium-dependent relaxation in aortae from spontaneously diabetic rats. Br J Pharmacol. 1988 Jun;94(2):463–468. doi: 10.1111/j.1476-5381.1988.tb11548.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dusting G. J., Mullins E. M., Nolan R. D. Prostacyclin (PGI2) release accompanying angiotensin conversion in rat mesenteric vasculature. Eur J Pharmacol. 1981 Mar 12;70(2):129–137. doi: 10.1016/0014-2999(81)90207-7. [DOI] [PubMed] [Google Scholar]
  6. Gebremedhin D., Koltai M. Z., Pogátsa G., Magyar K., Hadházy P. Influence of experimental diabetes on the mechanical responses of canine coronary arteries: role of endothelium. Cardiovasc Res. 1988 Aug;22(8):537–544. doi: 10.1093/cvr/22.8.537. [DOI] [PubMed] [Google Scholar]
  7. Ghahary A., Chakrabarti S., Sima A. A., Murphy L. J. Effect of insulin and statil on aldose reductase expression in diabetic rats. Diabetes. 1991 Nov;40(11):1391–1396. doi: 10.2337/diab.40.11.1391. [DOI] [PubMed] [Google Scholar]
  8. Gruetter C. A., Ryan E. T., Lemke S. M., Bailly D. A., Fox M. K., Schoepp D. D. Endothelium-dependent modulation of angiotensin II-induced contraction in blood vessels. Eur J Pharmacol. 1988 Jan 27;146(1):85–95. doi: 10.1016/0014-2999(88)90489-x. [DOI] [PubMed] [Google Scholar]
  9. Hattori Y., Kawasaki H., Abe K., Kanno M. Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta. Am J Physiol. 1991 Oct;261(4 Pt 2):H1086–H1094. doi: 10.1152/ajpheart.1991.261.4.H1086. [DOI] [PubMed] [Google Scholar]
  10. Hawthorne G. C., Bartlett K., Hetherington C. S., Alberti K. G. The effect of high glucose on polyol pathway activity and myoinositol metabolism in cultured human endothelial cells. Diabetologia. 1989 Mar;32(3):163–166. doi: 10.1007/BF00265088. [DOI] [PubMed] [Google Scholar]
  11. Jennings P. E., Barnett A. H. New approaches to the pathogenesis and treatment of diabetic microangiopathy. Diabet Med. 1988 Mar;5(2):111–117. doi: 10.1111/j.1464-5491.1988.tb00955.x. [DOI] [PubMed] [Google Scholar]
  12. Kern T. S., Engerman R. L. Immunohistochemical distribution of aldose reductase. Histochem J. 1982 May;14(3):507–515. doi: 10.1007/BF01011860. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Lagarde M., Burtin M., Berciaud P., Blanc M., Velardo B., Dechavanne M. Increase of platelet thromboxane A2 formation and of its plasmatic half-life in diabetes mellitus. Thromb Res. 1980 Sep 15;19(6):823–830. doi: 10.1016/0049-3848(80)90010-9. [DOI] [PubMed] [Google Scholar]
  15. Lubawy W. C., Valentovic M. Streptozocin-induced diabetes decreases formation of prostacyclin from arachidonic acid in intact rat lungs. Biochem Med. 1982 Dec;28(3):290–297. doi: 10.1016/0006-2944(82)90082-5. [DOI] [PubMed] [Google Scholar]
  16. Mayer J. H., Tomlinson D. R. Prevention of defects of axonal transport and nerve conduction velocity by oral administration of myo-inositol or an aldose reductase inhibitor in streptozotocin-diabetic rats. Diabetologia. 1983 Nov;25(5):433–438. doi: 10.1007/BF00282524. [DOI] [PubMed] [Google Scholar]
  17. Mayhan W. G., Simmons L. K., Sharpe G. M. Mechanism of impaired responses of cerebral arterioles during diabetes mellitus. Am J Physiol. 1991 Feb;260(2 Pt 2):H319–H326. doi: 10.1152/ajpheart.1991.260.2.H319. [DOI] [PubMed] [Google Scholar]
  18. McMillan D. E. The effect of diabetes on blood flow properties. Diabetes. 1983 May;32 (Suppl 2):56–63. doi: 10.2337/diab.32.2.s56. [DOI] [PubMed] [Google Scholar]
  19. Nakagawa M., Sawada S., Uno M., Takamatsu H., Nakamura Y., Nakanishi Y., Tsuji H., Toyoda T., Sasaki S., Takeda K. Effects of angiotensin I converting enzyme (ACE)-related substances on prostacyclin generation and ACE activity of human vascular endothelial cells and rat aortic rings. J Cardiovasc Pharmacol. 1987;10 (Suppl 7):S113–S115. doi: 10.1097/00005344-198706107-00022. [DOI] [PubMed] [Google Scholar]
  20. Ody C., Seillan C., Russo-Marie F., Duval D. Angiotensin II does not elicit any specific prostaglandin secretion in piglet cultured endothelial cells. Thromb Res. 1983 Jul 15;31(2):219–231. doi: 10.1016/0049-3848(83)90324-9. [DOI] [PubMed] [Google Scholar]
  21. Rasch R. Control of blood glucose levels in the streptozotocin diabetic rat using a long-acting heat-treated insulin. Diabetologia. 1979 Mar;16(3):185–190. doi: 10.1007/BF01219796. [DOI] [PubMed] [Google Scholar]
  22. Rosenblum W. I., Hirsh P. D. Some interrelationships between glucose levels thromboxane production and prostacyclin production in normal and diabetic mice. Prostaglandins. 1984 Jan;27(1):111–118. doi: 10.1016/0090-6980(84)90225-9. [DOI] [PubMed] [Google Scholar]
  23. Roth D. M., Reibel D. K., Lefer A. M. Vascular responsiveness and eicosanoid production in diabetic rats. Diabetologia. 1983 May;24(5):372–376. doi: 10.1007/BF00251827. [DOI] [PubMed] [Google Scholar]
  24. Rösen P., Schrör K. Increased prostacyclin release from perfused hearts of acutely diabetic rats. Diabetologia. 1980 May;18(5):391–394. doi: 10.1007/BF00276820. [DOI] [PubMed] [Google Scholar]
  25. Rösen P., Senger W., Feuerstein J., Grote H., Reinauer H., Schrör K. Influence of streptozotocin diabetes on myocardial lipids and prostaglandin release by the rat heart. Biochem Med. 1983 Aug;30(1):19–33. doi: 10.1016/0006-2944(83)90004-2. [DOI] [PubMed] [Google Scholar]
  26. Silberbauer K., Schernthaner G., Sinzinger H., Piza-Katzer H., Winter M. Decreased vascular prostacyclin in juvenile-onset diabetes. N Engl J Med. 1979 Feb 15;300(7):366–367. [PubMed] [Google Scholar]
  27. Takahashi K., Ghatei M. A., Lam H. C., O'Halloran D. J., Bloom S. R. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia. 1990 May;33(5):306–310. doi: 10.1007/BF00403325. [DOI] [PubMed] [Google Scholar]
  28. Takeda Y., Miyamori I., Yoneda T., Takeda R. Production of endothelin-1 from the mesenteric arteries of streptozotocin-induced diabetic rats. Life Sci. 1991;48(26):2553–2556. doi: 10.1016/0024-3205(91)90611-e. [DOI] [PubMed] [Google Scholar]
  29. Tooke J. E. Microcirculation and diabetes. Br Med Bull. 1989 Jan;45(1):206–223. doi: 10.1093/oxfordjournals.bmb.a072313. [DOI] [PubMed] [Google Scholar]
  30. Wakasugi M., Noguchi T., Inoue M., Tawata M., Shindo H., Onaya T. Effects of aldose reductase inhibitors on prostacyclin (PGI2) synthesis by aortic rings from rats with streptozotocin-induced diabetes. Prostaglandins Leukot Essent Fatty Acids. 1991 Dec;44(4):233–236. doi: 10.1016/0952-3278(91)90022-w. [DOI] [PubMed] [Google Scholar]
  31. Watts I. S., Zakrzewski J. T., Bakhle Y. S. Altered prostaglandin synthesis in isolated lungs of rats with streptozotocin-induced diabetes. Thromb Res. 1982 Nov 1;28(3):333–342. doi: 10.1016/0049-3848(82)90115-3. [DOI] [PubMed] [Google Scholar]
  32. Willars G. B., Calcutt N. A., Tomlinson D. R. Reduced anterograde and retrograde accumulation of axonally transported phosphofructokinase in streptozotocin-diabetic rats: effects of insulin and the aldose reductase inhibitor 'Statil'. Diabetologia. 1987 Apr;30(4):239–243. doi: 10.1007/BF00270422. [DOI] [PubMed] [Google Scholar]
  33. Williamson J. R., Chang K., Rowold E., Marvel J., Tomlinson M., Sherman W. R., Ackermann K. E., Kilo C. Sorbinil prevents diabetes-induced increases in vascular permeability but does not alter collagen cross-linking. Diabetes. 1985 Jul;34(7):703–705. doi: 10.2337/diab.34.7.703. [DOI] [PubMed] [Google Scholar]
  34. Williamson J. R., Kilo C. Capillary basement membranes in diabetes. Diabetes. 1983 May;32 (Suppl 2):96–100. doi: 10.2337/diab.32.2.s96. [DOI] [PubMed] [Google Scholar]
  35. Yorek M. A., Dunlap J. A. The effect of elevated glucose levels on myo-inositol metabolism in cultured bovine aortic endothelial cells. Metabolism. 1989 Jan;38(1):16–22. doi: 10.1016/0026-0495(89)90174-1. [DOI] [PubMed] [Google Scholar]
  36. Ziboh V. A., Maruta H., Lord J., Cagle W. D., Lucky W. Increased biosynthesis of thromboxane A2 by diabetic platelets. Eur J Clin Invest. 1979 Jun;9(3):223–228. doi: 10.1111/j.1365-2362.1979.tb00927.x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES