LACK OF CONTRIBUTION OF NITRIC-OXIDE TO BASAL VASOMOTOR TONE IN HEART-FAILURE

Patients with heart failure have reduced forearm vasodilator responses when endothelial cell nitric oxide production is stimulated by muscar inic ago nists. The aim of this study was to determine if activity of the nitric oxide pathway was also al, normal under basal conditions. F orearm blood flow (FBF) was measured with strain-gauge plethysmography in response to the intraarterial infusion of a subsystemic dose range of L-K monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. In 18 normal subjects, the baseline FBF of 3.6 +/- 1. 4 was de creased by 0.3 +/- 0.5 (p < 0.01), 1.0 +/- 0.7 (p < 0.01), 1. 4 +/- 0.9 (p < 0.01), and 1.3 +/- 1.3 (p < 0.01) ml/ min/100 ml forear m volume during infusions of 1, 4, 8, and 16 mu mol/min of L-NMMA, res pectively. In 10 patients with heart failure, the baseline FBF of 2.6 +/- 0.9 was decreased by 0.4 +/- 0.5 (p < 0.05), 0.4 +/- 0.5 (p < 0.05 ), 0.9 +/- 0.8 (p < 0.01), and 0.9 +/- 0.7 (p < 0.01) ml/min/100 ml fo rearm volume with the 4 doses of L-NMMA, respectively. There was no di fference in the L-NMMA response between the 2 groups in terms of absol ute now, percent change, or with analysis of covariance to adjust for different baselines. The stable end products of nitric oxide (nitrite and nitrate) were measured in the forearm venous effluent. Nitrite and nitrate levels at baseline were not reduced in patients with heart fa ilure. In addition, L-NMMA resulted in a similar decrease in levels fr om 106 +/- 36 to 93 +/- 44 mu M in normal subjects and from 152 +/- 31 to 130 +/- 31 mu M in patients with heart failure. This study demonst rates that the L-NMMA response in terms of the reduction in FBF and fo rearm venous nitrite and nitrate levels in patients with heart failure was comparable to that: in normal subjects. These data suggest that t he nitric oxide pathway in the forearm resistance vessels in heart fai lure is not impaired under basal conditions.