|
Sign In to gain access to subscriptions and/or personal tools.
|
Effect of angiotensin-converting enzyme inhibition on endothelial function and insulin sensitivity in hypertensive patients
Hakan Tezcan
Department of Internal Medicine, Marmara University School of Medicine, haktezcan{at}hotmail.com
Dilek Yavuz
Department of Internal Medicine, Marmara University School of Medicine
Ahmet Toprak
Department of Internal Medicine, Marmara University School of Medicine
Ihsan Akpmar
Department of Radiology, Marmara University School of Medicine, Istanbul, Turkey
Mehmet Koç
Department of Internal Medicine, Marmara University School of Medicine
Oguzhan Deyneli
Department of Internal Medicine, Marmara University School of Medicine
Sema Akalm
Department of Internal Medicine, Marmara University School of Medicine
Introduction
Evidence suggests an association between insulin resistance, hypertension and impaired endothelial function. Studies have shown that insulin resistance precedes the development of hypertension. By improving insulin sensitivity, it may be possible to improve hypertension and the subsequent damage to vessel walls. Some data indicates beneficial effects of angiotensin-converting enzyme (ACE) inhibitors on insulin sensitivity and endothelial function. We aimed to investigate these effects of ACE inhibition in the same group of patients with essential hypertension.
Materials and methods
Nine non-smoking, untreated hypertensive patients (38.3 9 years, 4/5 male/female) and 12 age-matched healthy subjects (35.2 6.7 years, 5/7 male/female) were included in the study. Hypertensive patients were given enalapril maleate (5—40 mg/day) for six months. The following parameters were studied at baseline and at the end of treatment period. Whole body insulin sensitivity was measured by a formula derived from an oral glucose tolerance test and named I as the insulin sensitivity index (ISI). Insulin was measured by chemiluminescence and glucose by a glucose oxidase method. Endothelial function was evaluated as flow-mediated dilatation (FMD) of the brachial artery by ultrasonography and expressed as a percentage change relative to baseline diameter. Endothelialindependent vasodilatation was measured after sublingual nitroglycerine.
Results
FMD was impaired in the hypertensive group compared with healthy subjects (7.3 3.1% vs. 15.3 4.8%, p<0.0005), and ISI values were 1.18 0.6 vs. 4.4 0.9 (p<0.0001) respectively. Both insulin sensitivity and FMD improved after the treatment period compared with baseline values, FMD increased from 7.3 3.1% to 16.0 2.9% (p<0.0005) and ISI from 1.18 0.6 to 4.2 1.0 (p<0.0001). FMD and ISI showed a significant positive correlation (r=0.67, p<0.001) in the hypertensive group.
Conclusions
Patients with essential hypertension have impaired endothelial function and decreased whole body insulin sensitivity compared with healthy subjects. Treatment for six months with enalapril maleate seems to improve both FMD and ISI. This study confirms the beneficial effects of ACE inhibition on both endothelial function and insulin sensitivity tested in the same group of essential hypertensive patients. The mechanism of these favourable effects of ACE inhibition needs to be clarified.
Key Words: ACE inhibition • endothelial dysfunction • insulin sensitivity
References
- Ferrannini E., Buzzigoli G., Bonadonna R. et al. Insulin resistance in essential hypertension.NEnglJMed 1987;317:350-7.[Abstract]
- Laakso M., Sarlund E., Mykkanen L. Essential hypertension and insulin resistance in non-insulin dependent diabetes. Eur J Clin Invest 1989;19:518-26.[Web of Science][Medline]
[Order article via Infotrieve]
- McLaughlin T., Reaven G. Insulin resistance and hypertension. Geriatrics 2000;55:28-33.[Web of Science][Medline]
[Order article via Infotrieve]
- Zavaroni I., Mazza S., Dall'Aglio E., Gasparini P., Passeri M., Reaven GM Prevalence of hyperinsulinaemia in patients with high blood pressure. J Intern Med 1992;231:235-40.[Web of Science][Medline]
[Order article via Infotrieve]
- Pinkney JH, Stehouwer CDA, Coppack SW, Yudkin JS Endothelial dysfunction: Cause of the insulin resistance syndrome. Diabetes 1997;46(suppl 2):S9-S12.[Web of Science][Medline]
[Order article via Infotrieve]
- Olsen MH,Andersen U.,Wachtell K., Ibsen H., Dige-Petersen H. A possible link between endothelial dysfunction and insulin resistance in hypertension. A Life substudy. Losartan Intervention For Endpoint-Reduction in Hypertension. Blood Press 2000;9:132-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Natali A., Taddei S., Galvan AQ et al. Insulin sensitivity, vascular reactivity, and clamp induced vasodilatation in essential hypertension. Circulation 1997;96:849-55.[Abstract/Free Full Text]
- Weir MR, Dzau VJ The renin-angiotensin-aldosterone system:A specific target for hypertension management. Am J Hypertension 1999;12:205S-213S.[Web of Science][Medline]
[Order article via Infotrieve]
- Cannon RO Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: the role of nitric oxide. Am J Cardiol 1998;82(10A): 8S-10S.[Web of Science][Medline]
[Order article via Infotrieve]
- Mancini GBJ, Henry GC, Macaya C. et al.Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease.The TREND Study. Circulation 1996;94:258-65.[Abstract/Free Full Text]
- Anderson TJ, Elstein E., Haber H., Charbonneau F. Comparative study of ACE-inhibition, angiotension II antagonism, and calcium channel blockade on flow-mediated vasodilation in patients with coronary disease (BANFF Study). J Am Coll Cardiol 1999;35:60-6.[Web of Science]
- O'Driscoll G., Green D., Rankin J., Stanton K., Taylor R. Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin-dependent diabetes mellitus. J Clin Invest 1997;100:678-84.[Web of Science][Medline]
[Order article via Infotrieve]
- Goto K., Fujii K., Onaka U., Abe I., Fujishima M. Renin angiotensin system blockade improves endothelial dysfunction in hypertension. Hypertension 2000;36:575-80.[Abstract/Free Full Text]
- Feldman RD, Schmidt ND Quinapril treatment enhances vascular sensitivity to insulin. J Hypertens 2001;19:113-18.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Ura N., Higashiura K., Shimamoto K. The mechanisms of insulin sensitivity improving effects of angiotensin converting enzyme inhibitor. Immunopharmacology 1999;44:153-9.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Akel A., Wiecek A., Nowicki M., Kokot F. The effect of treatment with enalapril versus losartan on levels of insulin resistance in patients with essential hypertension. Pol Arch Med Wewn 2000;103:123-31.[Medline]
[Order article via Infotrieve]
- Matsuda M., DeFronzo RA Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 1999;22:1462-70.[Abstract/Free Full Text]
- Celermajer DS, Sorensen KE, Gooch VM et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111-15.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Andersen TJ Assessment and treatment of endothelial dysfunction in humans. J Am Coll Cardiol 1999;34:631-8.[Free Full Text]
- Baumgartner-Parzer SM, Waldhausl WK The endothelium as a metabolic and endocrine organ: its relation with insulin resistance. Exp Clin Endocrinol Diabetes 2001;109(suppl 2): S166-S179.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Vane JR,Anggard EE, Botting RM Regulatory functions of the vascular endothelium. N Engl J Med 1990;323:27-36.[Web of Science][Medline]
[Order article via Infotrieve]
- Panza JA, Quyyumi AA, Brush JE, Epstein SE Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension.NEnglJMed 1990;323:22-7.[Abstract]
- Lembo G., Morella A., Lanni F., Rozza F., Trimarco B. Vascular insulin resistance in hypertension. Nutr Metab Cardiovasc Dis 1997;7:126-7.
- Reaven GM, Lithell H., Landsberg L. Hypertension and associated metabolic abnormalities - The role of insulin resistance and the sympathoadrenal system. N Engl J Med 1996;334:374-81.[Free Full Text]
- Cannon RO Potential mechanisms for the effect of angiotensin-converting enzyme inhibitors on endothelial dysfunction: the role of nitric oxide. Am J Cardiol 1998;82(10A): 8S-10S.[Web of Science][Medline]
[Order article via Infotrieve]
- Lonn EM,Yusuf S., Jha P. et al. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation 1994;90:2056-69.[Free Full Text]
- O'Driscoll G., Green D., Maiorana A., Stanton K., Colreavy F., Taylor R. Improvement in endothelial function by angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. J Am Coll Cardiol 1999;33:1506-11.[Abstract/Free Full Text]
- Wilmink HW, Banga JD, Hijmering M., Erkelens WD, Stroes ESG, Rabeling TJ Effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor antagonism on postprandial endothelial function. J Am Coll Cardiol 1999;34:1405.
- Cheetham C., Collis J., O'Driscoll G., Stanton K., Taylor R., Green D. Losartan, an angiotensin type 1 receptor antagonist, improves endothelial function in non-insulin-dependent diabetes. J Am Coll Cardiol 2000;36:1461-6.[Abstract/Free Full Text]
- Sun YPZhuBQ, Browne AE et al. Comparative effects of ACE inhibitors and an angiotensin receptor blocker on atherosclerosis and vascular function. J Cardiovasc Pharmacol Ther 2001;6:175-81.[Abstract/Free Full Text]
- Mullen MJ, Clarkson P., Donald AE et al. Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomised, double-blind study. J Am Coll Cardiol 1998;31:1330-5.[Abstract/Free Full Text]
- Hornig B.,Arakawa N., Haussmann D., Drexler H. Differential effects of quinaprilat and enalaprilat on endothelial function of conduit arteries in patients with chronic heart failure. Circulation 1998;98:2842-8.[Abstract/Free Full Text]
- Henriksen EJ, Jacob S., Augustin HJ, Dietze GJ Glucose transport activity in insulin resistant rat muscle. Diabetes 1996;45(suppl 1):S125-S128.[Web of Science][Medline]
[Order article via Infotrieve]
- Fogari R., Zoppi A., Preti P., Fogari E., Malamani G., Mugellini A. Differential effects of ACE-inhibition and angiotensin II antagonism on fibrinolysis and insulin sensitivity in hypertensive postmenopausal women. AmJHypertens 2001;14:921-6.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Muiesan ML, Salvetti M., Monteduro C. et al. Effect of treatment on flow-dependent vasodilation of the brachial artery in essential hypertension. Hypertension 1999;33: 575-80.[Abstract/Free Full Text]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 4, No. 2,
119-123 (2003)
DOI: 10.3317/jraas.2003.012
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
This article has been cited by other articles:
|
|
|
|
 
J.-C. Tardif
Angiotensin-converting enzyme inhibitors and atherosclerotic plaque: a key role in the cardiovascular protection of patients with coronary artery disease
Eur. Heart J. Suppl.,
August 1, 2009;
11(suppl_E):
E9 - E16.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
