Acetylcholine acutely modifies nitric oxide synthase function in the human coronary circulation.

Area of Science:

• Cardiovascular Physiology
• Endothelial Function Assessment
• Pharmacology of Coronary Circulation

Background:

• Acetylcholine (ACh) and N(G)-monomethyl-l-arginine (l-NMMA) are standard tools for evaluating endothelial function in coronary arteries.
• Previous research has not investigated whether responses to ACh predict responses to l-NMMA in individuals.

Purpose of the Study:

• To determine if human coronary vasomotor responses to intracoronary ACh infusions predict responses to intracoronary l-NMMA.
• To investigate the potential for ACh to acutely modify nitric oxide synthase (NOS) function.

Main Methods:

• Sequential intracoronary infusions of ACh and l-NMMA in 14 patients without severe coronary artery disease (CAD).
• Quantitative coronary angiography to measure changes in coronary diameter.
• Coronary sinus oxygen saturation and transcardiac oxygen saturation gradients to assess coronary blood flow (CBF).

Main Results:

• ACh significantly reduced coronary diameter and transcardiac oxygen saturation gradient.
• l-NMMA showed no significant effect on coronary diameter or transcardiac oxygen saturation gradient in patients without severe CAD.
• A positive correlation was found between ACh- and l-NMMA-induced changes in coronary diameter (r = 0.752, P = 0.0002).
• In patients with severe CAD, l-NMMA reduced CBF, indicating different responses compared to the ACh-treated group.

Conclusions:

• ACh administration may acutely impair NOS function in the human coronary circulation.
• The degree of NOS dysfunction appears directly correlated with the preceding ACh activation.
• These findings challenge the independent interpretation of ACh and l-NMMA tests for endothelial function assessment.