Nitric oxide release is impaired in hypertensive individuals with familial history of stroke.
BACKGROUND
A genetic origin of cerebrovascular accidents has long been suspected on the basis of epidemiologic evidence and familial aggregation. Nevertheless, the final phenotype is largely influenced by concomitant risk factors. We aimed to investigate whether impairment of endothelium-dependent vasodilation can be used as an informative intermediate vascular phenotype in hypertensive patients with familial history of stroke.


METHODS
Fourteen hypertensive individuals, seven with familial history of stroke (FH+), seven without familial history of stroke (FH-), and six normotensive volunteers (C) were included in the study. High-resolution ultrasound and Doppler were used to measure radial artery diameter and blood flow at rest, during reactive hyperemia, and after intra-arterial infusion of N(G)-monomethyl-l-arginine (L-NMMA) to inhibit NO synthase.


RESULTS
Basal blood flow and diameter were comparable in all groups. Flow-mediated dilation was impaired in FH+ (3.2% +/- 2%), compared with FH- (9.6% +/- 1%; P = . 01) and C (15.9% +/- 3%; P = . 001). The L-NMMA decreased basal flow in FH- (16.0 +/- 2 v 13.8 +/- 1 mL/min; P = . 04), and C (23.3 +/- 2 v 16.5 +/- 2 mL/min, P = .003) but did not exert any significant effect in FH+ subjects (16.4 +/- 3 v 15.8 +/- 2 mL/min, P = .77).


CONCLUSIONS
These findings demonstrate that NO bioavailability is reduced in hypertensive subjects with familial history of stroke. Such a phenotype may represent an early marker of susceptibility to cerebrovascular events in this population.
Cosentino
Francesco
F
Division of Cardiology, 2(nd) Faculty of Medicine, University La Sapienza, Rome, Italy.
Francia
Pietro
P
Musumeci
Beatrice
B
De Siati
Luca
L
Rao
Maria Assunta
MA
De Luca
Nicola
N
Balla
Cristina
C
De Sensi
Francesco
F
Volpe
Massimo
M
D000328:Adult; D001783:Blood Flow Velocity / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004791:Enzyme Inhibitors; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D006973:Hypertension / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin; D010375:Pedigree; D010641:Phenotype; D017534:Radial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology*; D020521:Stroke / Q000235:genetics*; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine
D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin