This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Voors, A. A Articles by van Gilst, W. H Search for Related Content PubMed PubMed Citation Articles by Voors, A. A Articles by van Gilst, W. H Social Bookmarking                         What's this?

Vascular effects of quinapril completely depend on ACE insertion/deletion polymorphism

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands, a.a.voors{at}thorax.azg.nl

Peter P van Geel

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Margreeth Oosterga

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Hendrik Buikema

Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

Dirk J van Veldhuisen

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands

Wiek H van Gilst

Department of Cardiology, Thoraxcenter, University Hospital Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB, Groningen, The Netherlands, Department of Clinical Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV, Groningen, The Netherlands

Introduction

The angiotensin-converting enzyme (ACE) DD-genotype is associated with increased plasma and myocardial ACE-activity. The influence of the ACE insertion/deletion (I/D) polymorphism on the effects of ACE-inhibition on vascular responses has not been previously described.

Materials and methods

In the randomised, double-blind QUinapril On Vascular ACE and Determinants of Ischemia Study (QUO VADIS), 149 patients undergoing coronary bypass surgery were randomised to receive either the ACE inhibitor, quinapril, or placebo. In 82 patients, we obtained ACE-genotype, and measured vascular responses to angiotensin II (Ang II) in left internal mammary arteries.

Results

In the placebo group, the mean maximal vasoconstriction to Ang II was significantly lower in patients with the DD-genotype than in those with the ID/II genotype (36.2±5.11% [n=13] vs. 55.6±4.57% [n=25]; p=0.01). In the quinapril group, the mean maximal vasoconstriction to Ang II was similar [n=8] vs. 57.7±4.07% [n=35]; p=0.85). between DD- and ID/II-genotype (59.6±9.19%

Conclusions

DD-genotype patients showed decreased vascular responses to Ang II but treatment with quinapril completely restored the decreased vascular response in DD-genotype patients to the same level as II/ID-genotype patients, while no effect of quinapril was demonstrated in the II/ID-genotype patients.

Key Words: angiotensin • arteries • bypass • vasoconstriction • vessels

References

• Tiret L., Rigat B., Visvikis S. et al. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 1992;51:197-205.[Web of Science][Medline] [Order article via Infotrieve]
• Davis GK, Millner RW, Roberts DH Angiotensin converting enzyme (ACE) gene expression in the human left ventricle: effect of ACE gene insertion/deletion polymorphism and left ventricular function. Eur J Heart Fail 2000;2:253-6.and left[Abstract/Free Full Text]
• Danser AH, Schalekamp MA, Bax WA et al. Angiotensin-convertin enzyme in the human heart. Effect of the deletion/insertion polymorphism. Circulation 1995;92:1387-8.[Abstract/Free Full Text]
• Sasaki M., Oki T., Iuchi A. et al. Relationship between the angiotensin converting enzyme gene polymorphism and the effects of enalapril on left ventricular hypertrophy and impaired diastolic filling in essential hypertension: M-mode and pulsed Doppler echocardiographic studies. J Hypertens 1996; 14:1403-08.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• NiuT., Chen X., Xu X. Angiotensin converting enzyme gene insertion/deletion polymorphism and cardiovascular disease: therapeutic implications. Drugs 2002;62:977-93.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Oosterga M., Voors AA, Buikema H. et al.Angiotensin II formation in human vasculature after chronic ACE inhibition: a prospective, randomized, placebo-controlled study. QUO VADIS Investigators. Cardiovasc Drugs Ther 2000;14:55-60.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Oosterga M., Voors AA, Pinto YM et al. Effects of quinapril on clinical outcome after coronary artery bypass grafting (The QUO VADIS Study). QUinapril on Vascular Ace and Determinants of Ischemia. Am J Cardiol 2001;87:542-6.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Voors AA, Pinto YM, Buikema H. et al. Dual pathway for angiotensin II formation in human internal mammary arteries. Br J Pharmacol 1998;125:1028-32.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Yang ZH, von Segesser L., Bauer E., Stulz P.,Turina M., Luscher TF Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein. Circ Res 1991;68:52-60.[Abstract/Free Full Text]
• Cushman DW, Cheung HS Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol 1971;20:1637-48.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ichiki T., Takeda K., Tokunou T. et al. Reactive oxygen species-mediated homologous downregulation of angiotensin II type 1 receptor mRNA by angiotensin II. Hypertension 2001;37(2 Part 2):535-40.[Abstract/Free Full Text]
• Lachurie ML,Azizi M., Guyene TT,Alhenc-Gelas F., Menard J. Angiotensin-converting enzyme gene polymorphism has no influence on the circulating renin-angiotensin-aldosterone system or blood pressure in normotensive subjects. Circulation 1995;91:2933-42.[Abstract/Free Full Text]
• van Dijk MA, Kroon I., Kamper AM, Boomsma F., Danser AH, Chang PCThe angiotensin-converting enzyme gene polymorphism and responses to angiotensins and bradykinin in the human forearm. J Cardiovasc Pharmacol 2000;35:484-90.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Ueda S., Elliott HL, Morton JJ, Connell JM Enhanced pressor response to angiotensin I in normotensive men with the deletion genotype (DD) for angiotensin-converting enzyme. Hypertension 1995;25:1266-9.[Abstract/Free Full Text]
• Gohlke P., Pees C., Unger T. AT2 receptor stimulation increases aortic cyclic GMP in SHRSP by a kinin-dependent mechanism. Hypertension 1998;31(1 Pt 2):349-55.[Abstract/Free Full Text]
• Stavroulakis GA, Makris TK, Krespi PG et al. Predicting response to chronic antihypertensive treatment with fosinopril: the role of angiotensin-converting enzyme gene polymorphism. Cardiovasc Drugs Ther 2000;14:427-32.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
• Todd GP, Chadwick IG, Higgins KS, Yeo WW, Jackson PR, Ramsay LE Relation between changes in blood pressure and serum ACE activity after a single dose of enalapril and ACE genotype in healthy subjects. Br J Clin Pharmacol 1995; 39:131-4.[Web of Science][Medline] [Order article via Infotrieve]
• O'Toole L., Stewart M., Padfield P., Channer K. Effect of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene on response to angiotensin-converting enzyme inhibitors in patients with heart failure. J Cardiovasc Pharmacol 1998;32:988-94.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 5, No. 3, 130-134 (2004)
DOI: 10.3317/jraas.2004.029


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Voors, A. A Articles by van Gilst, W. H Search for Related Content PubMed PubMed Citation Articles by Voors, A. A Articles by van Gilst, W. H Social Bookmarking                         What's this?