β2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans

Vesna D Garovic, Michael Joseph Joyner, Niki M. Dietz, Eric Boerwinkle, Stephen T Turner

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Polymorphisms in the gene encoding the β2-adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist-promoted downregulation of receptor expression in vitro. It is unknown whether genotype-dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β2-agonists in vivo. To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β-agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (±S.D.) = 29 ± 6 years), who were either Arg16 (n = 18) or Gly16 (n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol (P = 0.02). After inhibition of nitric oxide synthase by Nγ-monomethyl-L-arginine, blood flow responses did not differ significantly between genotype groups (P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β2-agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes.

Original languageEnglish (US)
Pages (from-to)583-589
Number of pages7
JournalJournal of Physiology
Volume546
Issue number2
DOIs
StatePublished - Jan 15 2003

Fingerprint

Homozygote
Isoproterenol
Forearm
Adrenergic Receptors
Nitric Oxide
Arginine
Genotype
Plethysmography
Brachial Artery
Regional Blood Flow
Vasodilator Agents
Nitric Oxide Synthase
Glycine
Down-Regulation
Blood Pressure
Hypertension
Amino Acids
Genes

ASJC Scopus subject areas

  • Physiology

Cite this

β2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans. / Garovic, Vesna D; Joyner, Michael Joseph; Dietz, Niki M.; Boerwinkle, Eric; Turner, Stephen T.

In: Journal of Physiology, Vol. 546, No. 2, 15.01.2003, p. 583-589.

Research output: Contribution to journalArticle

@article{958a0e816e374dcfb323356d3345407e,
title = "β2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans",
abstract = "Polymorphisms in the gene encoding the β2-adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist-promoted downregulation of receptor expression in vitro. It is unknown whether genotype-dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β2-agonists in vivo. To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β-agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (±S.D.) = 29 ± 6 years), who were either Arg16 (n = 18) or Gly16 (n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol (P = 0.02). After inhibition of nitric oxide synthase by Nγ-monomethyl-L-arginine, blood flow responses did not differ significantly between genotype groups (P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β2-agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes.",
author = "Garovic, {Vesna D} and Joyner, {Michael Joseph} and Dietz, {Niki M.} and Eric Boerwinkle and Turner, {Stephen T}",
year = "2003",
month = "1",
day = "15",
doi = "10.1113/jphysiol.2002.031138",
language = "English (US)",
volume = "546",
pages = "583--589",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - β2-Adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans

AU - Garovic, Vesna D

AU - Joyner, Michael Joseph

AU - Dietz, Niki M.

AU - Boerwinkle, Eric

AU - Turner, Stephen T

PY - 2003/1/15

Y1 - 2003/1/15

N2 - Polymorphisms in the gene encoding the β2-adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist-promoted downregulation of receptor expression in vitro. It is unknown whether genotype-dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β2-agonists in vivo. To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β-agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (±S.D.) = 29 ± 6 years), who were either Arg16 (n = 18) or Gly16 (n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol (P = 0.02). After inhibition of nitric oxide synthase by Nγ-monomethyl-L-arginine, blood flow responses did not differ significantly between genotype groups (P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β2-agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes.

AB - Polymorphisms in the gene encoding the β2-adrenoceptor have been associated with interindividual differences in blood pressure and the diagnosis of hypertension. A common polymorphism resulting in a change from arginine to glycine at amino acid 16 (Arg16 → Gly) enhances agonist-promoted downregulation of receptor expression in vitro. It is unknown whether genotype-dependent differences in nitric oxide generation contribute to differences in vasodilator responses to β2-agonists in vivo. To address this question, venous occlusion plethysmography was used to measure forearm blood flow responses to graded brachial artery infusions of the β-agonist isoproterenol in 41 healthy normotensive Caucasian adults (mean age (±S.D.) = 29 ± 6 years), who were either Arg16 (n = 18) or Gly16 (n = 23) homozygotes. Compared to Arg16 homozygotes, Gly16 homozygotes demonstrated significantly greater blood flow responses to isoproterenol (P = 0.02). After inhibition of nitric oxide synthase by Nγ-monomethyl-L-arginine, blood flow responses did not differ significantly between genotype groups (P = 0.27). Consequently, effects of the Arg16 → Gly polymorphism on forearm blood flow responses to isoproterenol appear to be dependent on differences in endothelial generation of nitric oxide. In contrast to previous reports based on systemic infusions of β2-agonists, our findings indicate that regional blood flow responses to locally infused isoproterenol are significantly greater in Gly16 than in Arg16 homozygotes.

UR - http://www.scopus.com/inward/record.url?scp=12244265520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12244265520&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2002.031138

DO - 10.1113/jphysiol.2002.031138

M3 - Article

C2 - 12527744

AN - SCOPUS:12244265520

VL - 546

SP - 583

EP - 589

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 2

ER -