Gly460Trp alpha-adducin gene polymorphism and endothelial function in untreated hypertensive patients.
OBJECTIVE
Endothelium-dependent vasodilatation is impaired in essential hypertension. Besides traditional and emerging cardiovascular risk factors, genetic factors may also promote deleterious alterations of endothelial physiology. The aim of the present study was to investigate the relationship between the 460Trp allele of ADD1 and endothelium-dependent vasodilation in 110 never-treated hypertensive patients.


METHODS
Forearm blood flow (FBF) was measured during intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) at increasing doses. Analysis of endothelium-dependent and endothelium-independent vasodilation was tested according to ADD1 genotype.


RESULTS
The FBF values at the three incremental doses of ACh were 5.22 +/- 0.24 (+76%), 8.64 +/- 0.45 (+193%) and 14.74 +/- 0.71 (+395%) ml/100 ml of tissue per min for Gly460Gly and 4.63 +/- 0.20 (+51%), 6.84 +/- 0.36 (+123%) and 11.22 +/- 3.8 (+269%) ml/100 ml of tissue per min for 460Trp. Thus, ACh-stimulated FBF was significantly reduced in hypertensive subjects carrying the 460Trp allele of ADD1 (P < 0.001). SNP-stimulated FBF was not affected by ADD1.


CONCLUSIONS
The main finding in this study was that in essential hypertensives the 460Trp allele of ADD1 is strongly associated with an impaired endothelium-dependent vasodilation, a powerful predictor of cardiovascular risk.
Perticone
Francesco
F
Department of Experimental and Clinical Medicine, University Magna Graecia, Catanzaro, Italy. perticone@unicz.it
Sciacqua
Angela
A
Barlassina
Cristina
C
Del Vecchio
Lucia
L
Signorello
Maria Chiara
MC
Dal Fiume
Chiara
C
Andreozzi
Francesco
F
Sesti
Giorgio
G
Cusi
Daniele
D
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005542:Forearm / Q000098:blood supply; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation; D000099291:Adducins
D000109:Acetylcholine; D002148:Calmodulin-Binding Proteins; D007703:Peptidyl-Dipeptidase A; D000099291:Adducins