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

Abhiram Prasad, Suresh Narayanan, Myron A. Waclawiw, Neal Epstein, Arshed A. Quyyumi

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

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. (C) 2000 by the American College of Cardiology.

Original languageEnglish (US)
Pages (from-to)1579-1586
Number of pages8
JournalJournal of the American College of Cardiology
Volume36
Issue number5
DOIs
StatePublished - Nov 1 2000
Externally publishedYes

Fingerprint

Peptidyl-Dipeptidase A
Blood Vessels
Nitric Oxide
Genes
Nitroprusside
Genotype
Acetylcholine
Alleles
Constriction
Arginine
Atherosclerosis
Angiotensin I
Angiotensin Type 1 Receptor
Vascular Smooth Muscle
Endothelium
Smooth Muscle
Coronary Artery Disease
Pathology
Incidence

ASJC Scopus subject areas

  • Nursing(all)

Cite this

The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. / Prasad, Abhiram; Narayanan, Suresh; Waclawiw, Myron A.; Epstein, Neal; Quyyumi, Arshed A.

In: Journal of the American College of Cardiology, Vol. 36, No. 5, 01.11.2000, p. 1579-1586.

Research output: Contribution to journalArticle

Prasad, Abhiram ; Narayanan, Suresh ; Waclawiw, Myron A. ; Epstein, Neal ; Quyyumi, Arshed A. / The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity. In: Journal of the American College of Cardiology. 2000 ; Vol. 36, No. 5. pp. 1579-1586.
@article{900a5bf1e8534fbd8eaf407ff13298dd,
title = "The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity",
abstract = "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. (C) 2000 by the American College of Cardiology.",
author = "Abhiram Prasad and Suresh Narayanan and Waclawiw, {Myron A.} and Neal Epstein and Quyyumi, {Arshed A.}",
year = "2000",
month = "11",
day = "1",
doi = "10.1016/S0735-1097(00)00902-5",
language = "English (US)",
volume = "36",
pages = "1579--1586",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "5",

}

TY - JOUR

T1 - The insertion/deletion polymorphism of the angiotensin-converting enzyme gene determines coronary vascular tone and nitric oxide activity

AU - Prasad, Abhiram

AU - Narayanan, Suresh

AU - Waclawiw, Myron A.

AU - Epstein, Neal

AU - Quyyumi, Arshed A.

PY - 2000/11/1

Y1 - 2000/11/1

N2 - 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. (C) 2000 by the American College of Cardiology.

AB - 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. (C) 2000 by the American College of Cardiology.

UR - http://www.scopus.com/inward/record.url?scp=0034332689&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034332689&partnerID=8YFLogxK

U2 - 10.1016/S0735-1097(00)00902-5

DO - 10.1016/S0735-1097(00)00902-5

M3 - Article

C2 - 11079661

AN - SCOPUS:0034332689

VL - 36

SP - 1579

EP - 1586

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 5

ER -