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Effects of common polymorphisms in the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoreceptors on haemodynamic responses to adrenaline

Snapir, A; Koskenvuo, J; Toikka, J; Orho-Melander, Marju LU ; Hinkka, S; Saraste, M; Hartiala, J and Scheinin, M (2003) In Clinical Science 104(5). p.509-520
Abstract
Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the... (More)
Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the alpha(1A)-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the alpha(2B)-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the beta(2)-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the alpha(2B)-AR D/D genotype confers increased vasoconstriction and that the beta(2)-AR GG genotype confers reduced vasodilatation. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
genetics, adrenaline, adrenoreceptors, in vivo, polymorphism
in
Clinical Science
volume
104
issue
5
pages
509 - 520
publisher
Portland Press
external identifiers
  • wos:000182738000007
  • pmid:12519093
  • scopus:0038017249
ISSN
1470-8736
DOI
10.1042/CS20020299
language
English
LU publication?
yes
id
6257ce00-bee7-4cb7-8288-5a2f355152e3 (old id 312153)
date added to LUP
2007-09-22 11:11:38
date last changed
2018-01-07 05:33:16
@article{6257ce00-bee7-4cb7-8288-5a2f355152e3,
  abstract     = {Common naturally occurring polymorphisms have been identified in the coding regions of the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoceptor (AR) genes [alpha(1A)-AR R492C, alpha(2B)-AR insertion/deletion (I/D), beta(1)-AR R389G, beta(2)-AR G16R and beta(2)-AR Q27E] and are associated with modified in vivo and in vitro functionality. We tested their possible effects on the haemodynamic responses to intravenous adrenaline (20, 40, 80 and 160 ng/kg of body weight per min; 5 min for each infusion rate) before and after beta-blockade (propranolol) in 16 young healthy men. We monitored changes in heart rate, blood pressure (BP), ECG, coronary flow velocity and plasma adrenaline and noradrenaline. The Cys/Cys (CC) genotype of the alpha(1A)-AR R492C polymorphism was associated with a longer ECG PR interval before and during the adrenaline infusions. The deletion/deletion (D/D) genotype of the alpha(2B)-AR I/D polymorphism was associated with blunted coronary blood flow increases during the adrenaline infusion before beta-blockade. The beta(1)-AR R389G polymorphism was not associated with modified responses to infused adrenaline. Subjects carrying the Gly/Gly (GG) genotype of the beta(2)-AR G16R polymorphism demonstrated increases in diastolic BP upon adrenaline infusion, whereas diastolic BP was decreased in the other genotype groups. These results suggest that, upon acute adrenaline infusion, the alpha(2B)-AR D/D genotype confers increased vasoconstriction and that the beta(2)-AR GG genotype confers reduced vasodilatation.},
  author       = {Snapir, A and Koskenvuo, J and Toikka, J and Orho-Melander, Marju and Hinkka, S and Saraste, M and Hartiala, J and Scheinin, M},
  issn         = {1470-8736},
  keyword      = {genetics,adrenaline,adrenoreceptors,in vivo,polymorphism},
  language     = {eng},
  number       = {5},
  pages        = {509--520},
  publisher    = {Portland Press},
  series       = {Clinical Science},
  title        = {Effects of common polymorphisms in the alpha(1A)-, alpha(2B)-, beta(1)- and beta(2)-adrenoreceptors on haemodynamic responses to adrenaline},
  url          = {http://dx.doi.org/10.1042/CS20020299},
  volume       = {104},
  year         = {2003},
}