Skip to main content

Advertisement

SpringerLink
Log in

Effects of blood pressure and glucose on endothelial function

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Hypertension and diabetes mellitus are associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Loss of the modulatory role of the endothelium can be considered the link between these conditions and cardiovascular disease. Substantial evidence suggests that vasodilation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models and in patients with hypertension and diabetes mellitus. NO is a principal factor involved in the anti-atherosclerotic properties of the endothelium. Therefore, the pathogenesis of hypertensive and diabetic vascular disease may involve a reduced bioavailability of endothelium-derived NO. Inactivation of NO by reactive oxygen species is an important common mechanism by which endothelial dysfunction may occur. This review summarizes experimental and clinical evidence for impaired NO-mediated vasodilation in the presence of high blood pressure and hyperglycemia. A better understanding of the mechanisms leading to endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbility and mortality in these conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Furchgott RF, Zawadzki JV: The obligatory role of endothelial cells in the relaxation of arterial smooth muscle to acetylcholine. Nature 1980, 288:373–376.

    Article  PubMed  CAS  Google Scholar 

  2. Cosentino F, Luscher TF: Maintenance of vascular integrity: role of nitric oxide and other bradykinin mediators. Eur Heart J 1995, 16(K):4–12.

    PubMed  CAS  Google Scholar 

  3. MacMahon S, Peto R, Cutler J, et al.: Blood pressure, stroke and coronary heart disease. Part I: Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 1990, 335:765–774.

    Article  PubMed  CAS  Google Scholar 

  4. Kannel WB, McGee DL: Diabetes and cardiovascular disease: the Framingham study. JAMA 1978, 241:2035–2038.

    Article  Google Scholar 

  5. Laasko M, Lehto S: Epidemiology of macrovascular disease in diabetes. Diab Rev 1997, 5:294–315.

    Google Scholar 

  6. Laasko M: Hyperglycemia and cardiovascular disease in type 2 diabetes. Diabetes 1999, 48:937–948.

    Article  Google Scholar 

  7. Rees DD, Palmer RMJ, Moncada S: Role of endotheliumderived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci U S A 1989, 86:3375–3378.

    Article  PubMed  CAS  Google Scholar 

  8. Ross R: The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993, 362:801–809.

    Article  PubMed  CAS  Google Scholar 

  9. Cosentino F, Luscher TF: Tetrahydrobiopterin and endothelial nitric oxide synthase activity. Cardiovasc Res 1999, 43:274–278.

    Article  PubMed  CAS  Google Scholar 

  10. Wever RMF, Luscher TF, Cosentino F, et al.: Atherosclerosis and the two faces of endothelial nitric oxide synthase. Circulation 1998, 97:108–112. This paper reviews the current concept that eNOS may play a dual role in the pathogenesis of atherosclerosis: under normal conditions, through the generation of NO, it favors an anti-atherosclerotic environment. However, in the presence of risk factors, it may contribute to oxidative stress. Furthermore, it emphasizes the role of redox state as a determinant of vascular integrity in atherosclerosis.

    PubMed  CAS  Google Scholar 

  11. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991, 43:109–142.

    PubMed  CAS  Google Scholar 

  12. Luscher TF, Vanhoutte PM: The Endothelium: Modulator of Cardiovascular Function. Boca Raton, FL: CRC Press; 1990.

    Google Scholar 

  13. Kelm M, Feelisch M, Krebber T, et al.: The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats. J Cardiovasc Pharmacol 1992, 20:183–186.

    Google Scholar 

  14. Nava E, Noll G, Luscher TF: Increased activity of constitutive nitric oxide synthase in cardiac endothelium in spontaneous hypertension. Circulation 1995, 91:2310–2323.

    PubMed  CAS  Google Scholar 

  15. Nakazono K, Watanabe N, Matsuno K, et al.: Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci U S A 1991, 88:10045–10048.

    Article  PubMed  CAS  Google Scholar 

  16. Cosentino F, Patton S, d‘Uscio LV, et al.: Tetrahydrobiopterin alters superoxide and nitric oxide release in prehypertensive rats. J Clin Invest 1998, 101:1530–1537. This paper supports the concept that a higher production of reactive oxygen species generated via a dysfunctional eNOS may contribute to the development of hypertension and its complications.

    PubMed  CAS  Google Scholar 

  17. Moreau P, Takase H, Kung CF, et al.: Blood pressure and vascular effects of endothelin blockade in chronic nitric oxide-deficient hypertension. Hypertension 1997, 29:763–769.

    PubMed  CAS  Google Scholar 

  18. Linder L, Kiowski W, Buhler FR, et al.: Indirect evidence for the release of endothelium-derived relaxing factor in the human forearm circulation in vivo: blunted response in hypertension. Circulation 1990, 81:1762–1767.

    PubMed  CAS  Google Scholar 

  19. Panza JA, Quyyumi AA, Brush JH Jr, et al.: Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 1990, 323:22–27.

    Article  PubMed  CAS  Google Scholar 

  20. Treasure CB, Manoukian SV, Klein GL, et al.: Epicardial coronary artery responsee to acetylcholine are impaired in hypertensive patients. Circ Res 1992, 71:776–781.

    PubMed  CAS  Google Scholar 

  21. Egashira K, Suzuki S, Hirooka Y, et al.: Impaired endotheliumdependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Circulation 1995, 25:201–206.

    CAS  Google Scholar 

  22. Li J, Zaho SP, Li XP, et al.: Non-invasive detection of endothelial dysfunction in patients with essential hypertension. Int J Cardiol 1997, 61:165–169.

    Article  PubMed  CAS  Google Scholar 

  23. Forte P, Copland M, Smith LM, et al.: Basal nitric oxide synthesis in essential hypertension. Lancet 1997, 349:837–842.

    Article  PubMed  CAS  Google Scholar 

  24. Cockroft JR, Chowienczyck PJ, Benjamin N, et al.: Preserved endothelium-dependent vasodilation in patients with essential hypertension. N Engl J Med 1994, 300:1036–1040.

    Article  Google Scholar 

  25. Brunig TA, Chang PC, Hendricks GC, et al.: In vivo characterization of muscarinic receptors subtypes that mediate vasodilation in patients with essential hypertension. Hypertension 1995, 26:70–77.

    Google Scholar 

  26. Taddei S, Virdis A, Mattei P, et al.: Vasodilation to acetylcholine in primary and secondary forms of hypertension. Hypertension 1993, 21:929–933.

    PubMed  CAS  Google Scholar 

  27. Taddei S, Virdis A, Mattei P, et al.: Hypertension causes premature aging of endothelial function in humans. Hypertension 1997, 29:736–743.

    PubMed  CAS  Google Scholar 

  28. Taddei S, Virdis A, Ghiadoni L, et al.: Cyclooxygenase inhibition restores nitric oxide activity in essential hypertension. Hypertension 1997, 29:274–279.

    PubMed  CAS  Google Scholar 

  29. Solzbach U, Horning B, Jeserisch M, et al.: Vitamin C improves endothelial dysfunction of epicardial coronary arteries in hypertensive patients. Circulation 1997, 96:1513–1519.

    PubMed  CAS  Google Scholar 

  30. Taddei S, Virdis A, Mattei P, et al.: Defective l-arginine-nitric oxide pathway in offspring of essential hypertensive patients. Circulation 1996, 94:1298–1303.

    PubMed  CAS  Google Scholar 

  31. Tesfamariam B, Jakubowski JA, Cohen RA: Contraction of diabetic rabbit aorta due to endothelium-derived PGH2/ TXA2. Am J Physiol 1989, 257:H13272-H13277.

    Google Scholar 

  32. Mayhan W, Simmons LK, Sharpe QM: Mechanisms of impaired responses of cerebral arterioles during diabetes mellitus. Am J Physiol 1991, 260:H319-H326.

    PubMed  CAS  Google Scholar 

  33. Tesfamariam B, Brown ML, Deykin D, et al.: Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest 1990, 85:929–932.

    PubMed  CAS  Google Scholar 

  34. Tesfamariam B, Brown ML, Cohen RA: Elevated glucose impairs endothelium-dependent relaxation by activating protein chinase C. J Clin Invest 1991, 87:1643–1648.

    Article  PubMed  CAS  Google Scholar 

  35. Tesfamariam B, Cohen RA: Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Physiol 1992, 263:H321-H323.

    PubMed  CAS  Google Scholar 

  36. Hattori Y, Kawasaki H, Abe K, et al.: Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta. Am J Physiol 1991, 261:H1086-H1094.

    PubMed  CAS  Google Scholar 

  37. Saenz de Tejada I, Goldstein I, Azadzoi K, et al.: Impaired neurogenic and endothelium-dependent relaxation of human penile smooth muscle: the pathophysiological basis for impotence in diabetes mellitus. N Engl J Med 1989, 320:1025–1030.

    Article  PubMed  CAS  Google Scholar 

  38. Calver A, Collier J, Vallance P: Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes. J Clin Invest 1992, 90:2548–2554.

    PubMed  CAS  Google Scholar 

  39. Elliot TG, Cockroft JR, Groop PH, et al.: Inhibition of nitric oxide synthesis in forearm vasculature of insulin dependent patients: blunted vasoconstriction in patients with microalbuminuria. ClinSci 1993, 85:687–693.

    Google Scholar 

  40. Johnstone MT, Craeger SJ, Scales KM, et al.: Impaired endothelium-dependent vasodilation in patients with insulindependent diabetes mellitus. Circulation 1993, 88:2510–2516.

    PubMed  CAS  Google Scholar 

  41. McVeigh GE, Brennan GM, Johnston BJ, et al.: Impaired endothelium-dependent and -independent vasodilation in patients with type 2 diabetes mellitus. Diabetologia 1992, 35:771–776.

    PubMed  CAS  Google Scholar 

  42. Enderle MD, Benda N, Schmuelling RM, et al.: Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects. Diabetes Care 1998, 21:271–277.

    Article  PubMed  CAS  Google Scholar 

  43. Arcaro G, Zenere BM, Saggiani F, et al.: ACE inhibitors improve endothelial function in type 1 diabetic patients with normal arterial pressure and microalbuminuria. Diabetes Care 1999, 22:1536–1542.

    Article  PubMed  CAS  Google Scholar 

  44. Ting HH, Timimi FK, Boles KS, et al.: Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus. J Clin Invest 1996, 97:22–28.

    PubMed  CAS  Google Scholar 

  45. Timimi FK, Ting HH, Haley EA, et al.: Vitamin C improves endothelium-dependent vasodilation in patients with insulin-dependent diabetes mellitus. J Am Coll Cardiol 1998, 31:552–557. Short-term administration of vitamin C improves endotheliumdependent vasodilation in patients with insulin-dependent diabetes mellitus, supporting the hypothesis that oxidative stress underlies hyperglycemia-induced endothelial dysfunction.

    Article  PubMed  CAS  Google Scholar 

  46. Cosentino F, Hishikawa K, Katusic ZS, et al.: High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 1997, 96:25–28.

    PubMed  CAS  Google Scholar 

  47. Tesfamariam B: Free radicals in diabetic endothelial dysfunction. Free Radic Biol Med 1994, 16:383–391.

    Article  PubMed  CAS  Google Scholar 

  48. Katusic ZS, Schugel J, Cosentino F, et al.: Endotheliumdependent contractions to oxygen-derived free radicals in canine basilar arteries. Am J Physiol 1993, 264:H859-H864.

    PubMed  CAS  Google Scholar 

  49. Koya D, King GL: Protein kinase C activation and the development of diabetic complications. Diabetes 1998, 47:859–866. This paper discusses the link between oxidative stress and protein kinase C pathway and its crucial importance in determining hyperglycemia-induced endothelial dysfunction.

    Article  PubMed  CAS  Google Scholar 

  50. Wu KK, Hatsakis H, Lo SS, et al.: Stimulation of de novo synthesis of prostaglandin G/H synthase in human endothelial cells by phorbol esters. J Biol Chem 1988, 263:19043–19047.

    PubMed  CAS  Google Scholar 

  51. Robinson JM, Badwey JA, Karnovski ML, et al.: Superoxide release by neutrophils: synergistic effects of a phorbol ester and a calcium ionophore. Biochem Biophys Res Commun 1984, 122:734–739.

    Article  PubMed  CAS  Google Scholar 

  52. Miyata T, Van Ypersele de Strihou C, Kurokawa K, et al.: Alterations in nonenzymatic biochemistry in uremia: origin and significance of “carbonyl stress” in long term uremic complications. Kidney Int 1999, 55:389–399.

    Article  PubMed  CAS  Google Scholar 

  53. Schmidt AM, Yan SD, Wautier JL, et al.: Activation of receptor for advance glycation end products. A mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 1999, 84:489–497.

    PubMed  CAS  Google Scholar 

  54. Vlassara H, Fuh H, Makita Z, et al.: Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and ageing complications. Proc Natl Acad Sci U S A 1992, 89:12043–12047.

    Article  PubMed  CAS  Google Scholar 

  55. Braunwald E: Heart Disease. Philadelphia: WB Saunders; 1997.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Cardiology and Cardiovascular Research, University Hospital, Ramistrasse 100, CH-8091, Zurich, Switzerland

    Francesco Cosentino MD, PhD & Thomas F. Lüscher MD

  2. IRCCS Neuromed, via Atinense 18, Pozzilli (IS), Italy

    Francesco Cosentino MD, PhD

Authors
  1. Francesco Cosentino MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas F. Lüscher MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cosentino, F., Lüscher, T.F. Effects of blood pressure and glucose on endothelial function. Current Science Inc 3, 79–88 (2001). https://doi.org/10.1007/s11906-001-0085-8

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-001-0085-8

Keywords

Search

Navigation