Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Nov;89(3):613–618. doi: 10.1111/j.1476-5381.1986.tb11163.x

Changes in cardiovascular sensitivity of alloxan-treated diabetic rats to arachidonic acid.

A L Boura, W C Hodgson, R G King
PMCID: PMC1917153  PMID: 3099877

Abstract

Arachidonic acid (AA, 0.125-2.0 mg kg-1) administered intravenously to male Wistar rats produced a dose-dependent fall in diastolic blood pressure. However AA (0.125-1.0 mg kg-1) injected into the autoperfused hindquarters via the aorta produced a dose-dependent increase in perfusion pressure. Both these responses to AA were inhibited by indomethacin (5 mg kg-1). The thromboxane A2 receptor antagonist AH23848 (5 mg kg-1, i.v.) inhibited pressor responses to AA in the autoperfused hindquarters, but potentiated depressor responses to AA (0.125-0.5 mg kg-1) in the whole animal. Alloxan-treated diabetic rats (14 days after a single s.c. injection of alloxan, 175 mg kg-1) displayed reduced sensitivity to the depressor effects of AA (1-2 mg kg-1) in the whole animal, increased sensitivity to the pressor effects of AA (0.5-1.0 mg kg-1) in the perfused hindquarters, and reduced sensitivity to the pressor effects of the thromboxane A2 mimetic U46619 (0.5-8.0 micrograms kg-1, i.a.) in the perfused hindquarters. These results suggest that AA can be predominantly converted to either pressor or depressor metabolites depending on the vasculature. In the diabetic state the ratio of the metabolites formed appears to change favouring a major pressor metabolite, which is probably thromboxane A2.

Full text

PDF
613

Selected References

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

  1. Belo S. E., Talesnik J. Coronary vasoconstrictor and vasodilator actions of arachidonic acid in the isolated perfused heart of the rat. Br J Pharmacol. 1982 Feb;75(2):269–286. doi: 10.1111/j.1476-5381.1982.tb08783.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Canga L., Sterin-Borda L., Borda E. S., Peredo H., Gimeno A. L. The positive inotropic effect of sodium arachidonate on auricles from diabetic rats. Eur J Pharmacol. 1985 Mar 26;110(1):47–54. doi: 10.1016/0014-2999(85)90027-5. [DOI] [PubMed] [Google Scholar]
  3. Coleman R. A., Humphrey P. P., Kennedy I., Levy G. P., Lumley P. U-46619, a selective thromboxane A2-like agonist? [proceedings]. Br J Pharmacol. 1980 Jan;68(1):127P–128P. [PMC free article] [PubMed] [Google Scholar]
  4. Gerrard J. M., Stuart M. J., Rao G. H., Steffes M. W., Mauer S. M., Brown D. M., White J. G. Alteration in the balance of prostaglandin and thromboxane synthesis in diabetic rats. J Lab Clin Med. 1980 Jun;95(6):950–958. [PubMed] [Google Scholar]
  5. Gilbert V. A., Zebrowski E. J., Chan A. C. Differential effects of megavitamin E on prostacyclin and thromboxane synthesis in streptozotocin-induced diabetic rats. Horm Metab Res. 1983 Jul;15(7):320–325. doi: 10.1055/s-2007-1018709. [DOI] [PubMed] [Google Scholar]
  6. Halushka P. V., Rogers R. C., Loadholt C. B., Colwell J. A. Increased platelet thromboxane synthesis in diabetes mellitus. J Lab Clin Med. 1981 Jan;97(1):87–96. [PubMed] [Google Scholar]
  7. Harrison H. E., Reece A. H., Johnson M. Decreased vascular prostacyclin in experimental diabetes. Life Sci. 1978 Jul 24;23(4):351–355. doi: 10.1016/0024-3205(78)90020-6. [DOI] [PubMed] [Google Scholar]
  8. Harrison H. E., Reece A. H., Johnson M. Effect of insulin treatment on prostacyclin in experimental diabetes. Diabetologia. 1980 Jan;18(1):65–68. doi: 10.1007/BF01228305. [DOI] [PubMed] [Google Scholar]
  9. Johnson M., Harrison H. E., Raftery A. T., Elder J. B. Vascular prostacyclin may be reduced in diabetes in man. Lancet. 1979 Feb 10;1(8111):325–326. doi: 10.1016/s0140-6736(79)90737-2. [DOI] [PubMed] [Google Scholar]
  10. Quilley J., McGiff J. C. Arachidonic acid metabolism and urinary excretion of prostaglandins and thromboxane in rats with experimental diabetes mellitus. J Pharmacol Exp Ther. 1985 Jul;234(1):211–216. [PubMed] [Google Scholar]
  11. 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]
  12. Rösen P., Hohl C. Prostaglandins and diabetes. Ann Clin Res. 1984;16(5-6):300–313. [PubMed] [Google Scholar]
  13. 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]
  14. Sterin-Borda L., Gimeno M., Borda E., del Castillo E., Gimeno A. L. Prostacyclin (PGI2) and U-46619 stimulate coronary arteries from diabetic dogs and their action is influenced by inhibitors of prostaglandin biosynthesis. Prostaglandins. 1981 Aug;22(2):267–278. doi: 10.1016/0090-6980(81)90041-1. [DOI] [PubMed] [Google Scholar]
  15. Subbiah M. T., Dietemeyer D. Altered synthesis of prostaglandins in platelet and aorta from spontaneously diabetic Wistar rats. Biochem Med. 1980 Apr;23(2):231–235. doi: 10.1016/0006-2944(80)90076-9. [DOI] [PubMed] [Google Scholar]
  16. Valentovic M. A., Lubawy W. C. Impact of insulin or tolbutamide treatment on 14C-arachidonic acid conversion to prostacyclin and/or thromboxane in lungs, aortas, and platelets of streptozotocin-induced diabetic rats. Diabetes. 1983 Sep;32(9):846–851. doi: 10.2337/diab.32.9.846. [DOI] [PubMed] [Google Scholar]
  17. Vigo C., Lewis G. P., Piper P. J. Mechanisms of inhibition of phospholipase A2. Biochem Pharmacol. 1980 Feb 15;29(4):623–627. doi: 10.1016/0006-2952(80)90386-x. [DOI] [PubMed] [Google Scholar]
  18. 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