Lack of association between endothelial nitric oxide synthase gene polymorphisms, microalbuminuria and endothelial dysfunction in hypertensive men.
BACKGROUND
The Glu298Asp, T786C and 4a/4b genetic polymorphisms within the endothelial nitric oxide synthase (e-NOS) gene may predispose to hypertension, ischaemic heart disease and renal damage, possibly by reducing the generation of nitric oxide (NO), a fundamental substance in renal and cardiovascular biology. That same mechanism may contribute to raise albuminuria, a correlate of endothelial dysfunction and a marker of early kidney damage and poor cardiovascular prognosis in patients with hypertension. To assess that hypothesis, we evaluated the association of albuminuria with eNOS genotypes and their interacting potential with the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We also tested their impact on systemic NO availability, as reflected by endothelial-mediated forearm vasodilatation.


METHODS
Albuminuria (three overnight collections), blood pressure, body mass index, renal function, glucose, lipids and prevalence of the metabolic syndrome were measured in 235 genetically unrelated, never-treated, uncomplicated white men with essential hypertension. Endothelial function was assessed in a patient subgroup (n = 94) by measuring plethysmographic forearm blood flow vasodilatation in response to intra-arterial acetylcholine with sodium nitroprusside as a control. Polymerase chain reaction or a 5' nuclease assay were used to characterize the eNOS and ACE I/D variants.


RESULTS
Albuminuria or microalbuminuria (albuminuria > or = 15 microg/min) showed no association with eNOS polymorphisms either per se or after accounting for the co-existing ACE I/D genetic configuration. Forearm responses to acetylcholine did not differ by eNOS polymorphisms. Cardiovascular, renal, metabolic parameters were homogeneously distributed across different genetic backgrounds.


CONCLUSIONS
eNOS polymorphisms apparently play no role in promoting hypertensive renal damage, and do not influence endothelial-mediated vasodilatation in never-treated men with essential hypertension.
Dell'Omo
Giulia
G
Department of Cardiothoracics, University of Pisa, Pisa, Italy.
Penno
Giuseppe
G
Pucci
Laura
L
Fotino
Carmen
C
Lucchesi
Daniela
D
Del Prato
Stefano
S
Pedrinelli
Roberto
R
D000419:Albuminuria / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D004730:Endothelium, Vascular; D005542:Forearm; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012867:Skin / Q000098:blood supply; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III