85007
document
Altered peripheral vasodilator profile of nitroglycerin during long-term infusion of N-acetylcysteine . OBJECTIVES The aim of this study was to compare the short- and long-term effects of intravenous nitroglycerin plus placebo and nitroglycerin plus N-acetylcysteine on peripheral arteries , veins and microcirculation in humans . BACKGROUND The thiol donor N-acetylcysteine may potentiate the hemodynamic response to nitrates in nitrate-tolerant and nontolerant patients . The vascular changes responsible for this effect are not clear . METHODS Eight male volunteers were treated with nitroglycerin ( 0.1 microgram/kg per min ) combined with N-acetylcysteine ( 2 g intravenously , followed by 5 mg/kg per h ) or placebo for 23 h in a double-blind , randomized , crossover study . Venous volume , the diameter of the radial and temporal arteries , calf blood flow and subcutaneous blood flow were measured at baseline and repeated after 1 and 23 h of infusion . RESULTS Prolonged coadministration of N-acetylcysteine and nitroglycerin potentiated the acute venodilator effect of nitroglycerin as estimated by changes in venous volume ( nitroglycerin plus N-acetylcysteine , 4.45 +/- 0.36 ml/100 g ; nitroglycerin plus placebo , 3.65 +/- 0.46 ml/100 g , mean +/- SEM , p < 0.05 ) and prevented development of tolerance as seen after 23 h of treatment with nitroglycerin plus placebo ( 4.35 +/- 0.25 vs. 3.47 +/- 0.41 ml/100 g , p < 0.05 ) . N-acetylcysteine had no effect on nitroglycerin-induced changes in arterial diameters ( p > 0.05 ) but significantly increased microcirculatory subcutaneous blood flow after 1 h ( nitroglycerin plus N-acetylcysteine : 6.3 +/- 1.3 ml/100 g per min vs. nitroglycerin plus placebo : 3.5 +/- 0.3 ml/100 g per min , p < 0.05 ) and after 23 h ( 4.4 +/- 0.6 vs. 3.1 +/- 0.5 ml/100 g per min , p < 0.05 ) . CONCLUSIONS The results suggest that coadministration of nitroglycerin and N-acetylcysteine in humans 1 ) potentiates and preserves nitroglycerin-induced venodilation and 2 ) augments the effect of nitroglycerin on small resistance vessels ( regulating subcutaneous blood flow ) without affecting the response to nitroglycerin in middle-sized arteries . Both the development of nitrate tolerance and the administration of N-acetylcysteine significantly change the normal vasodilator profile of nitroglycerin in humans .
85008
Intervention_Control
intravenous nitroglycerin plus placebo
85009
Intervention_Pharmacological
nitroglycerin plus N-acetylcysteine
85010
Intervention_Pharmacological
N-acetylcysteine
85011
Intervention_Pharmacological
nitroglycerin ( 0.1 microgram/kg per min )
85012
Intervention_Pharmacological
N-acetylcysteine
85013
Intervention_Control
placebo
85014
Intervention_Pharmacological
N-acetylcysteine and nitroglycerin
85015
Intervention_Pharmacological
nitroglycerin plus N-acetylcysteine
85016
Intervention_Control
nitroglycerin plus placebo
85017
Intervention_Pharmacological
N-acetylcysteine
85018
Intervention_Pharmacological
nitroglycerin-induced
85019
Intervention_Pharmacological
nitroglycerin plus N-acetylcysteine
85020
Intervention_Pharmacological
nitroglycerin plus placebo
85021
Intervention_Pharmacological
nitroglycerin and N-acetylcysteine
85022
Intervention_Pharmacological
nitroglycerin-induced
85023
Intervention_Pharmacological
N-acetylcysteine
85024
Intervention_Pharmacological
nitroglycerin
85025
Outcome_Physical
peripheral vasodilator profile
85026
Outcome_Physical
short- and long-term effects
85027
Outcome_Physical
Venous volume
85028
Outcome_Physical
diameter of the radial and temporal arteries , calf blood flow
85029
Outcome_Physical
subcutaneous blood flow
85030
Outcome_Physical
acute venodilator effect
85031
Outcome_Physical
changes in venous volume
85032
Outcome_Mental
development of tolerance
85033
Outcome_Physical
nitroglycerin-induced changes in arterial diameters
85034
Outcome_Other
microcirculatory subcutaneous blood flow after 1 h
85035
Outcome_Physical
nitroglycerin-induced venodilation
85036
Outcome_Physical
effect of nitroglycerin on small resistance vessels
85037
Outcome_Other
(
85038
Outcome_Physical
regulating subcutaneous blood flow
85039
Outcome_Other
) without affecting the response to nitroglycerin in middle-sized arteries .
85040
Outcome_Physical
nitrate tolerance
85041
Outcome_Physical
vasodilator profile
85042
Participant_Sample-size
Eight
85043
Participant_Sex
male