Altered beta-2 adrenergic receptor gene expression in human clinical hypertension.
OBJECTIVE
The beta-2 adrenergic receptor is involved in mediating vasodilatation via neurohumoral and sympathetic nervous system pathways. Alterations in beta-2 adrenergic receptor gene expression (mRNA transcription) may contribute to the hypertensive phenotype. Human gene expression in clinical phenotypes remains largely unexplored due to ethical constraints involved in obtaining human tissue. We devised a method to obtain normally discarded internal mammary artery tissue from coronary artery bypass graft patients. We then investigated differences in hypertensive and normotensive participants' beta-2 adrenergic receptor gene expression in this tissue.


METHODS
We collected arterial tissue samples from 46 coronary artery bypass patients in a surgical setting. Using 41 of the samples, we performed TaqMan real-time polymerase chain reaction (RT-PCR) and used the delta delta cycle threshold (DeltaDeltaCt) relative quantitation method for determination of fold-differences in gene expression between normotensive and hypertensive participants. The beta-2 adrenergic receptor target was normalized to glyceraldehyde-phosphate dehydrogenase.


RESULTS
Participants with hypertension had significantly less-expressed beta-2 adrenoceptor gene (2.76-fold, p<.05) compared to normotensive participants. After Bonferroni correction, gene expression did not differ by race, gender, type/dose of beta-blocker prescribed, positive family history of hypertension, or diagnosis of diabetes mellitus type 2.


CONCLUSIONS
These data support the possibility of a molecular basis for impaired adrenoceptor-mediated vascular tone in hypertension. Modification and extension of this research is required.
Dungan
Jennifer R
JR
Duke University School of Nursing, Durham, North Carolina 27710, USA. jennifer.dungan@duke.edu
Conley
Yvette P
YP
Langaee
Taimour Y
TY
Johnson
Julie A
JA
Kneipp
Shawn M
SM
Hess
Philip J
PJ
Yucha
Carolyn B
CB
D016022:Case-Control Studies; D015400:Clinical Nursing Research; D001026:Coronary Artery Bypass; D015987:Effect Modifier, Epidemiologic; D005260:Female; D005431:Florida; D015870:Gene Expression / Q000235:genetics*; D005820:Genetic Testing; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D008297:Male; D008323:Mammary Arteries / Q000166:cytology / Q000637:transplantation; D008875:Middle Aged; D015999:Multivariate Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018709:Statistics, Nonparametric; D014158:Transcription, Genetic / Q000235:genetics
D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases