Related Experiment Videos
Nitric oxide production is maintained in exercising swine with chronic left ventricular dysfunction
David B Haitsma1, Daphne Merkus, Jefrey Vermeulen
1Experimental Cardiology, Thoraxcenter, Erasmus University, Rotterdam, The Netherlands.
Summary
Following myocardial infarction (MI), nitric oxide (NO) availability is reduced, impairing vasodilation. However, NO
Area of Science:
- Cardiovascular Physiology
- Endothelial Function
- Myocardial Infarction Research
Background:
- Left ventricular (LV) dysfunction post-myocardial infarction (MI) is linked to endothelial dysfunction and reduced nitric oxide (NO) availability.
- Impaired tissue perfusion during exercise in MI patients may stem from endothelial dysfunction.
- The role of NO in regulating vascular tone during exercise in the context of LV dysfunction requires further investigation.
Purpose of the Study:
- To test if endothelial dysfunction contributes to impaired tissue perfusion during exercise in swine with LV dysfunction due to MI.
- To determine the contribution of NO to systemic, pulmonary, and coronary vasomotor tone regulation in exercising swine with LV dysfunction post-MI.
Main Methods:
- Utilized swine models with induced LV dysfunction via a 2-3 week old MI.
- Administered N(omega)-nitro-L-arginine (L-NNA) to block NO synthase and aminoguanidine to selectively inhibit inducible NO synthase.
- Measured systemic, pulmonary, and coronary vascular responses to ATP, nitroprusside, and during treadmill exercise.
Main Results:
- LV dysfunction blunted ATP-induced systemic and coronary vasodilation, but nitroprusside responses were preserved.
- Exercise induced blunted systemic and pulmonary vasodilation in MI swine, similar to NO synthase blockade in normal swine.
- NO synthase inhibition (L-NNA) similarly reduced vascular conductance in normal and MI swine at rest and during exercise.
- Selective inhibition of inducible NO synthase had no effect on vascular tone in MI swine.
Conclusions:
- Agonist-induced vasodilation is impaired early after myocardial infarction.
- Endothelial NO synthase-derived NO's contribution to vascular tone regulation is maintained under basal and exercise conditions post-MI.
- Despite reduced NO availability, the NO pathway remains functional for maintaining vascular tone during increased metabolic demand post-MI.