Eicosanoids and Diabetic Hypertension

  • K. Schrör
Conference paper


Hypertension is more common in juvenile onset diabetes than in the normal population and is considered to be a major risk factor in this group of patients (Christlieb et al. 1981). More than 2.5 million Americans suffer from diabetes associated with hypertension (Working Group on Hypertension in Diabetes 1987). The development of the vascular complications of diabetes, namely diabetic macro- and microangiopathy and the prothrombotic stage, eventually combined with diabetic hypertension, might be facilitated by a more general disturbance in the defence mechanisms of the body, being related to insulin deficiency. This involves alterations in eicosanoid production that are not only important for control of insulin secretion (Rösen and Hohlfeld 1985; Robertson 1986) but also for the vascular and thrombotic complications of the disease. This paper reviews the present evidence for a contribution of disturbed eicosanoid production to the vascular complications in diabetes mellitus with particular emphasis on hypertension.


Diabetic Subject Diabetic Ketoacidosis Tail Artery Eicosanoid Production Lipoxygenase Product 
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  1. Aanderud S, Krane H, Nordoy A (1985) Influence of glucose, insulin and sera from diabetic patients on the prostacyclin synthesis in vitro in cultured human endothelial cells. Diabetologia 28: 641–644PubMedCrossRefGoogle Scholar
  2. Arisaka M, Arisaka O, Fukuda Y, Yamashiro Y (1986) Prostaglandin metabolism in children with diabetes mellitus: I. Plasma prostaglandin E2, F2α, TXB2, and serum fatty acid levels. J Pediatr Gastroenterol Nutr 5: 878–882PubMedCrossRefGoogle Scholar
  3. Axelrod L, Shulman Gl, Blackshear PJ, Borastein M, Roussell AM, Aoki TT (1986) Plasma level of 13,14-düiydro-15-keto-PGE2 in patients with diabetic ketoacidosis and in normal fasting subjects. Diabetes 35: 1004–1010PubMedCrossRefGoogle Scholar
  4. Bresser H-J, Rösen P, Schrör K (1987) Insulin treatment normalizes the arachidonie acid induced prostacyclin release from the platelet-perfused diabetic rat heart. Evidence for major changes in 15- HETE production. In: Sinzinger H, Sehrör K (eds) Prostaglandins in Clinical Research Alan R. Liss, Inc. New York, p 143–148Google Scholar
  5. Broderick R, Tulenko T (1983) Cholesterol increases noradrenalin ( NE) sensitivity in perfused rabbit femoral arteries. Fed Proc 42: 1387Google Scholar
  6. Brunner D, Klinger J, Weisbort J, Tuval M, Nakash J, Rosenberg CH, Nissim S (1984) Thromboxane, prostacyclin, beta-thromboglobin, and diabetes mellitus. Clin Ther 6: 636–642PubMedGoogle Scholar
  7. Christlieb AR, Warram JH, Kodewski AS, Busick EJ, Guanda OP, Asmal AC, Soeldner JS (1981) Hypertension: the major risk factor in juvenile onset insulin dependent diabetics. Diabetes 30 [Suppl 2]: 90–96PubMedGoogle Scholar
  8. Collier A, Tymkewycz P, Armstrong R, Young RJ, Jones RL, Clarke BF (1986) Increased platelet thromboxane receptor sensitivity in diabetic patients with proliferative retinopathy. Diabetologia 29: 471–474PubMedCrossRefGoogle Scholar
  9. Colwell JA, Winocour PD, Halushka PV (1983) Do platelets have anything to do with diabetic microvascular disease? Diabetes 32 [Suppl 2]: 14–19PubMedGoogle Scholar
  10. Davis TM, Bown E, Turner RC (1985) Platelet sensitivity in vitro to adenosine-5-diphosphate and prostacyclin and diabetic retinopathy. Diabetologia 28: 274–276PubMedCrossRefGoogle Scholar
  11. Esmatjes E, Fernandez MR, Halperin I, Camps J, Gaya J, Arroyo V, Rivera F, Figuerola D (1985) Renal hemodynamic abnormalities in patients with short term insulin-dependent diabetes mellitus: role of renal prostaglandins. J. Clin Endocrinol Metab 60: 1231–1236PubMedCrossRefGoogle Scholar
  12. Feigl W, Sinzinger H, Santler R, Oppolzer R, Silberbauer K (1986) In vitro Prostaglandin I2-Synthese normaler und pathologisch veränderter menschlicher Beinvenen. Vasa 15: 47–51PubMedGoogle Scholar
  13. Funakawa S, Okahara T, Imanishi M, Komori T, Yamamoto K, Tochino Y (1983) Renin-angiotensin system and prostacyclin biosynthesis in streptozotocin diabetic rats. Eur J Pharmacol 94: 27–33PubMedCrossRefGoogle Scholar
  14. Guicheney P, Baudoin-Legros M, Meyer P (1987) Study of in vivo platelet activation in uncomplicated essential hypertension. Thromb Res 40: 615–621Google Scholar
  15. Halushka PV, Rogers RC, Loadhold CB, Colwell JA (1981) Increased platelet-thromboxane synthesis in diabetes mellitus. J Lab Clin Med 97: 87–96PubMedGoogle Scholar
  16. Harrison HE, Reece AH, Johnson M (1978) Decreased vascular prostacyclin in experimental diabetes. Life Sci 23: 351–356PubMedCrossRefGoogle Scholar
  17. Harrison HE, Reece AH, Johnson M (1980) Effect of insulin treatment on prostacyclin in experimental diabetes. Diabetologia 18: 65–68PubMedCrossRefGoogle Scholar
  18. Hayashi M, Senba S, Saito I, Kitajima W, Saruta T (1983) Changes in blood pressure, urinary kallikrein, and urinary prostaglandin E2 in rats with streptozotocin-induced diabetes. Naunyn- Schmiedebergs Arch Pharmacol 322: 290–294PubMedCrossRefGoogle Scholar
  19. Inoguchi T, Umeda F, Watanabe J, Ibayashi H (1986) Reduced serum-stimulatory activity on prostacyclin production by cultured aortic endothelial cells in diabetes mellitus. Haemostasis 16: 447–452PubMedGoogle Scholar
  20. Johnson M, Harrison HE, Raftery AT, Eldor JB (1979) Vascular prostacyclin may be reduced in diabetes in man. Lancet i: 325–326Google Scholar
  21. Jones DB, Carter RD, Haitas B, Mann JI (1983) Low phospholipid arachidonic acid values in diabetic platelets. Br Med J 286: 173CrossRefGoogle Scholar
  22. Karpen CW, Cataland S, O’Dorisio CM, Panganamala RV (1985) Production of 12-hydroxyeicosatetraenoic acid and vitamin E status in platelets from type I human diabetic subjects. Diabetes 34: 526–531Google Scholar
  23. Katayama S, Lee JB (1985) Hypertension in experimental diabetes mellitus. Renin-prostaglandin interaction. Hypertension 7: 554–561PubMedGoogle Scholar
  24. Katayama S, Inaba M, Maruno Y, Omoto A, Kawazu S, Ishii J (1987) Increased thromboxane B2 excretion in diabetes mellitus. J Lab Clin Med 109: 711–717PubMedGoogle Scholar
  25. Komori T, Fujii S, Nogi O, Ohashi M, Sasakawa O, Yamamoto K (1985) Prostacyclin production reduced in diabetics with vascular complications. Jpn J Med 24: 231–235PubMedCrossRefGoogle Scholar
  26. Kubisz P, Arabi A, Holan J, Cronberg S (1984) Investigations on platelet function in diabetes mellitus. Haemostasis 14: 347 - 353PubMedGoogle Scholar
  27. Lagarde M, Burtin M, Berciaud P, Blanc M, Velardo B, Dechavanne M (1980) Increase of thromboxane A2 formation and of its plasmatic half life in diabetes mellitus. Thromb Res 19: 823–830PubMedCrossRefGoogle Scholar
  28. Lucas FV, Skrinska VA, Chisolm GM, Hesse BL (1986) Stability of prostacyclin in human and rabbit whole blood and plasma. Thromb Res 43: 379–387PubMedCrossRefGoogle Scholar
  29. MacLeod KM, McNeill JH (1985) The influence of chronic experimental diabetes on contractile response of rat isolated blood vessels. Can J Physiol Pharmacol 63: 52–57PubMedCrossRefGoogle Scholar
  30. McNamara DB, Donath GR, Kadowitz PJ, Hyman AL, Rush DS, Kerstein MD (1986) Prostacyclin synthetase activity in human diabetic and nondiabetic vascular tissue. J Vase Surg 4: 63–67Google Scholar
  31. McRae JR, Day RP, Metz SA, Halter JB, Ensinck JW, Robertson RP (1985) Prostaglandin E2 metabolicte levels during diabetic ketoacidosis. Diabetes 34: 761–766PubMedCrossRefGoogle Scholar
  32. Metz SA, Rice MG, Robertson RP (1979) Application and limitations of measurements of 15-keto- 13,14-dihydro-prostaglandinE2 in human blood by radioimmunoassay. Prostaglandins 17: 839–861PubMedCrossRefGoogle Scholar
  33. Mourits:Andersen T, Jensen R, Dyerberg J (1986) Plasma prostaglandins: 6-keto-PGFla, TXB2 and PGE2 in juvenile-onset diabetes determined by high-pressure liquid chromatography and radioimmunoassay. Prostaglandins Leukotrienes Med 22: 335–348Google Scholar
  34. Müller SM, Müller TM, Ertel PJ (1982) Sympathetic and vascular dysfunction in early experimental juvenile diabetes mellitus. Am J Physiol 243: H139–H144Google Scholar
  35. O’Malley BC, Timperly WR, Ward JD, Porter NR (1975) Platelet abnormalities in diabetic peripheral neuropathy. Lancet ii: 1274–1276Google Scholar
  36. Pfaffman MA, Ball CR, Darby A, Hilman R (1982) Insulin reversal of diabetes-induced inhibition of vascular contractility in the rat. Am J Physiol 242: H490–H495PubMedGoogle Scholar
  37. Pottathil R, Huang SW, Chandrabose KA (1985) Essential fatty acids in diabetes and systemic lupuserythematosus (SLE) patients. Biochem Biophys Res Commun 128: 803-808 Quilley J, McGiff JC (1986) Influence of insulin on urinary eicosanoid excretion in rats with experi¬mental diabetes mellitus. J. Pharmacol Exp Ther 238: 606–611Google Scholar
  38. Ramanadham S, Lyness WH, Tenner TE (1983) Alterations in aortic and tail artery reactivity after streptozotocin treatment. Can J Physiol Pharmacol 62: 418–423CrossRefGoogle Scholar
  39. Robertson RP (1986) Arachidonic acid metabolite regulation of insulin secretion. Diabetes Metab Rev 2: 261–296PubMedCrossRefGoogle Scholar
  40. Rosen P, Hohlfeld C (1984) Prostaglandins and diabetes. Ann Clin Res 16: 300–313PubMedGoogle Scholar
  41. Saroyan RM, Kerstein MD, Kadowitz PJ, Hyman AL, McNamara DB (1984) Prostacyclin synthetase activity in diabetic human venous tissue. Surgery 96: 179–183PubMedGoogle Scholar
  42. Sensaki S, Okuma M, Uchino H (1985) Decreased plasma prostacyclin-regenerating activities in diabetics. Prostaglandins Leukotrienes Med 20: 197–207CrossRefGoogle Scholar
  43. Setty BN, Stuart MJ (1986) 15-Hydroxy-5,8,11,13-eicosatetraenoic acid inhibits human vascular cyclooxygenase. Potential role in diabetic vascular disease. J Clin Invest 77: 202–211Google Scholar
  44. Shakir KM, Reed HL, O’Brian JT (1986) Decreased phospholipase A2 activity in plasma and liver in uncontrolled diabetes mellitus. A defect in the early steps of prostaglandin synthesis? Diabetes 35: 403–410PubMedCrossRefGoogle Scholar
  45. Silberbauer K, Schernthaner G, Sinzinger H, Pitza-Katzer H, Winter M (1979) Decreased vascular prostacyclin in juvenile-onset diabetes. New Engl J Med 300: 366–367PubMedGoogle Scholar
  46. Wakabayashi I, Hatake K, Kimura N, Kakishita E, Nagai K (1987) Modulation of vascular tonus by the endothelium in experimental diabetes. Life Sci 40: 643–648PubMedCrossRefGoogle Scholar
  47. Wiles PG, Johnson M (1985) Plasma prostacyclin-stimulating activity in diabetes mellitus. Horm Metab Res 17: 610–611PubMedCrossRefGoogle Scholar
  48. Wilson TW, Tan LK (1985) Low plasma renin activity in diabetes. Relation to urine prostaglandin excretion. Diabetes 34: 145–150PubMedCrossRefGoogle Scholar
  49. Working Group on Hypertension in Diabetes (1987) Statement on hypertension in diabetes mellitus. Arch Intern Med 147: 830–842CrossRefGoogle Scholar
  50. Zatz R, Brenner BM (1986) Pathogenesis of diabetic microangiopathy. The hemodynamic view. Am J Med 80: 443–453PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1988

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  • K. Schrör

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