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 agonists. The aim of this study was to determine if activity of the nitric oxide pathway was also abnormal 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-N-monomethylarginine (L-NMMA), a competitive inhibitor of nitric oxide synthase. In 18 normal subjects, the baseline FBF of 3.6 +/- 1.4 was decreased 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 mumol/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 flow, 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Heart Failure-Heart Transplantation Program, University of Minnesota Medical School, Minneapolis.
S H
SH
Kubo
T S
TS
Rector
A J
AJ
Bank
L
L
Raij
M D
MD
Kraemer
P
P
Tadros
M
M
Beardslee
M D
MD
Garr
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010991:Plethysmography / Q000379:methods; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine