Polymorphic variant endothelial nitric oxide synthase impairs endothelium dependent vascular relaxation in both heterozygotes and homozygotes

The G894T mutation of eNOS has been associated with vascular disease in homozygotes. Comparison of changes in forearm vascular resistance to ACh (endothelial dependent vasodilator) and nitroprusside (endothelium independent) in 19 healthy subjects, four of whom (21%) were heterozygous (GT) and six (32%) of whom were homozygous (TT). Forearm vascular resistance using venous occlusion plethysmography in both homozygotes (TT) and heterozygotes showed ED50 of ACh was significantly higher than that for the wild type (11.4±2.55 and 10.7±4.39 vs 3.36±0.61 respectively, p<0.001), with no difference between the two groups carrying the T allele. ED50 for SNP was comparable in the three groups (GG 0.62±0.090, GT 0.90±0.82, TT 0.73±0.55, p>0.05). The T allele is associated with impaired relaxation in both heterozygotes and homozygotes.