This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Prasad, A. Articles by Quyyumi, A. A. Search for Related Content PubMed PubMed Citation Articles by Prasad, A. Articles by Quyyumi, A. A.

CLINICAL STUDY

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity

^a Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA

Manuscript received November 9, 1999; revised manuscript received April 17, 2000, accepted June 15, 2000.

Reprint requests and correspondence: Dr. Arshed A. Quyyumi, National Institutes of Health, Cardiology Branch, NHLBI, Bldg. 10, Rm. 7B15, 10 Center Dr. MSC 1650, Bethesda, Maryland 20892-1650
quyyumia{at}nih.gov

OBJECTIVES

We investigated whether the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene modulates vasomotor tone and endothelial function.

BACKGROUND

The deletion allele of the ACE I/D polymorphism has been associated with increased incidence of cardiovascular pathology. The risk is synergistically increased in patients who also possess the C allele at position 1,166 of the angiotensin type I (AT1) receptor gene.

METHODS

In 177 patients with coronary atherosclerosis or its risk factors, we investigated endothelial function with intracoronary acetylcholine (ACH), endothelium-independent smooth muscle function with sodium nitroprusside (SNP) and basal nitric oxide activity with L-N^G monomethyl arginine.

RESULTS

Compared with ACE II genotype, patients with the ACE DD genotype had lower coronary microvascular and epicardial responses with SNP (coronary blood flow increase 196 ± 26% vs. 121 ± 11%, p = 0.003, and diameter increase 21.9 ± 2% vs. 17 ± 1%, p = 0.03, ACE II vs. DD, respectively). L-N^G monomethyl arginine induced greater constriction in patients with the ACE DD compared with ACE II genotype (coronary blood flow –10 ± 4% vs. 11 ± 5%, p = 0.003, ACE DD vs. II and diameter constriction –6.3 ± 1.2% vs. –1.9 ± 1.2%, p = 0.01, respectively, in patients with atherosclerosis). No difference in ACH-mediated vasomotion was detected between the three ACE genotypes. The AT1 receptor polymorphism did not influence responses to either SNP or ACH.

CONCLUSIONS

Patients possessing the D allele of the ACE gene have increased vascular smooth muscle tone. The enhanced tone appears to be counterbalanced by an increase in basal nitric oxide activity in patients with atherosclerosis.

Abbreviations and Acronyms   A/C = adenine/cytosine   ACE = angiotensin-converting enzyme   ACH = acetylcholine   ANOVA = analysis of variance   AT1 = angiotensin type I   CAD = coronary artery disease   D = deletion   I = insertion   L-NMMA = L-NG monomethyl arginine   MI = myocardial infarction   NO = nitric oxide   PCR = polymerase chain reaction   SNP = sodium nitroprusside

This article has been cited by other articles:

				J. W Olin Masterclass series in peripheral arterial disease: Hypertension and peripheral arterial disease Vascular Medicine, August 1, 2005; 10(3): 241 - 246. [PDF]

				P. Di Pasquale, S. Cannizzaro, and S. Paterna Does angiotensin-converting enzyme gene polymorphism affect blood pressure? Findings after 6 years of follow-up in healthy subjects Eur J Heart Fail, January 1, 2004; 6(1): 11 - 16. [Abstract] [Full Text] [PDF]

				S Gulec, O Aras, Y Atmaca, O Akyurek, N Q Hanson, T Sayin, M Y Tsai, N Akar, and D Oral Deletion polymorphism of the angiotensin I converting enzyme gene is a potent risk factor for coronary artery ectasia Heart, February 1, 2003; 89(2): 213 - 214. [Full Text] [PDF]

				S. Kennon, K. Barakat, G. A. Hitman, C. P. Price, P. G. Mills, K. Ranjadayalan, J. Cooper, H. Clark, and A. D. Timmis Angiotensin-converting enzyme inhibition is associated with reduced troponin release in non-ST-elevation acute coronary syndromes J. Am. Coll. Cardiol., September 1, 2001; 38(3): 724 - 728. [Abstract] [Full Text] [PDF]

				A. Prasad, S. Husain, W. Schenke, R. Mincemoyer, N. Epstein, and A. A. Quyyumi Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans J. Am. Coll. Cardiol., November 1, 2000; 36(5): 1467 - 1473. [Abstract] [Full Text] [PDF]