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Nitric oxide inhibition impairs blood flow during exercise in hearts with a collateral-dependent myocardial region
J H Traverse1, J W Kinn, C Klassen
1Department of Medicine, University of Minnesota Medical School and Minneapolis Heart Institute 55455, USA.
Insights
Nitric oxide (NO) is crucial for maintaining coronary blood flow during exercise in hearts with collateral vessels. Blocking NO reduces blood flow in both collateral and normal regions during exertion.
Area of Science:
- Cardiovascular Physiology
- Exercise Physiology
- Myocardial Perfusion
Background:
- Coronary collateral vessels exhibit NO-dependent vasodilation.
- The role of endogenous NO in collateral function during exercise was previously unstudied.
Purpose of the Study:
- To determine the importance of nitric oxide (NO) production in maintaining coronary blood flow during exercise in hearts with collateral-dependent myocardium.
Main Methods:
- Collateral vessel growth was induced in dogs via coronary artery occlusion.
- Myocardial blood flow was measured at rest and during exercise before and after NO blockade with N-nitro-L-arginine (LNNA).
Main Results:
- NO blockade significantly reduced coronary blood flow to collateral-dependent regions during exercise.
- LNNA increased collateral vascular resistance and decreased blood flow in normal myocardial regions during exercise.
- NO blockade inhibited acetylcholine-induced coronary vasodilation by 62%.
Conclusions:
- Endogenous NO production is vital for maintaining coronary collateral blood flow during exercise.
- NO also supports blood flow in remote myocardial regions during exercise in the presence of coronary occlusion.
- Myocardial blood flow regulation during exercise differs in normal versus collateral-dependent hearts.
Objectives:
We sought to determine the importance of nitric oxide (NO) production in maintaining coronary blood flow during exercise in hearts with collateral-dependent myocardium.
Background:
Coronary collateral vessels demonstrate endothelium-mediated NO-dependent vasodilation in response to agonists such as acetylcholine. However, the contribution of endogenous NO production to maintaining vasodilation of coronary collateral vessels during exercise has not been previously studied.
Methods:
Collateral vessel growth was induced in 13 chronically instrumented dogs by intermittent 2-min occlusions, followed by permanent occlusion of the left anterior descending coronary artery (LAD). One week after permanent LAD occlusion, myocardial blood flow was measured with microspheres during rest and treadmill exercise at 6.4 km/h at a 15% grade. Measurements were then repeated after blockade of NO production with N-nitro-L-arginine (LNNA) (20 mg/kg body weight intravenously).
Results:
LNNA caused a 62 +/- 4% (mean +/- SEM) inhibition of the coronary vasodilation produced by acetylcholine. During rest conditions, LNNA caused a slight decrease in blood flow to the collateral region (p = NS), with no change in normal zone blood flow. During exercise, LNNA caused a decrease in mean blood flow to the collateral region (from 2.24 +/- 0.19 to 1.78 +/- 0.26 ml/min per g after LNNA, p < 0.05). This decrease resulted from a near doubling of the collateral vascular resistance (p < 0.05), with a trend toward an increase in small vessel resistance in the collateral zone. LNNA also reduced myocardial blood flow to the normal region during exercise (from 2.99 +/- 0.24 to 2.45 +/- 0.28 ml/min per g, p < 0.05) as the result of a 44 +/- 13% increase in coronary vascular resistance (p < 0.05).
Conclusions:
NO contributes to the maintenance of coronary collateral blood flow during exercise. In contrast to the normal heart, endogenous NO production also maintains blood flow in remote myocardial regions during exercise. These results suggest that control of blood flow during exercise in normal myocardium is altered by the presence of an occluded coronary artery.