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 muscarinic ago nists. The aim of this study was to determine if activity of the nitric oxide pathway was also al, normal under basal conditions. Forearm 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 forearm volume during infusions of 1, 4, 8, and 16 mu mol/min of L-NMMA, respectively. 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 forearm volume with the 4 doses of L-NMMA, respectively. There was no difference in the L-NMMA response between the 2 groups in terms of absolute 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 failure. In addition, L-NMMA resulted in a similar decrease in levels from 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 demonstrates that the L-NMMA response in terms of the reduction in FBF and forearm venous nitrite and nitrate levels in patients with heart failure was comparable to that: in normal subjects. These data suggest that the nitric oxide pathway in the forearm resistance vessels in heart failure is not impaired under basal conditions.