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.