Evidence supporting abnormalities in nitric oxide synthase function induced by nitroglycerin in humans

Area of Science:

• Cardiovascular Physiology
• Endothelial Function
• Pharmacology

Background:

• Nitroglycerin (GTN) therapy may alter endothelial cell function, increasing superoxide production and vasoconstrictor sensitivity.
• Continuous GTN use has been shown to worsen endothelial function in coronary circulation for patients with ischemic heart disease.

Purpose of the Study:

• To investigate the impact of continuous nitroglycerin (GTN) therapy on forearm vascular responses to endothelium-dependent and independent agents in healthy individuals.
• To assess potential endothelial dysfunction and alterations in nitric oxide synthase (NOS) activity induced by GTN treatment.

Main Methods:

• A randomized, parallel-design study involving 16 healthy male volunteers.
• Participants received either no therapy (control) or continuous GTN (0.6 mg/h/24 h) for six days.
• Forearm blood flow was measured using mercury-in-silastic strain gauge plethysmography during brachial artery infusions of acetylcholine, N-monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP).

Main Results:

• GTN therapy significantly blunted vasodilator responses to acetylcholine (endothelium-dependent) compared to controls (p < 0.05).
• Vasoconstrictor responses to L-NMMA (NOS inhibition) were also blunted in the GTN group (p < 0.001), with paradoxical vasodilation observed at the lowest L-NMMA concentration.
• Vasodilator responses to sodium nitroprusside (SNP, endothelium-independent) did not differ between the GTN and control groups.

Conclusions:

• Continuous GTN therapy induces endothelial dysfunction in healthy subjects, supporting the study's hypothesis.
• GTN treatment appears to cause abnormalities in nitric oxide synthase (NOS) function.
• The paradoxical vasodilation suggests a potential NOS-mediated production of a vasoconstrictor associated with continuous GTN therapy.