Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia

Abstract

Background - Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production or is influenced by adrenergic mechanisms. Methods and yResults - In 12 healthy men, myocardial perfusion was measured with PET in 2 protocols performed in random order, each including 3 perfusion measurements. First, perfusion was measured at rest. Second, either saline or the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was determined. Last, in both protocols, the α-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined again. Resting perfusion was similar in the 2 protocols (0.69±0.14 and 0.66±0.18 mL · min-1 · g-1). L-NAME increased mean arterial blood pressure by 12±7 mm Hg (P<0.01) and reduced heart rate by 16±7 bpm (P<0.01). Adenosine-induced hyperemia (1.90±0.33 mL · min-1 · g-1) was attenuated by L-NAME (1.50±0.55 mL · min-1 · g-1, P<0.01). The addition of phentolamine had no effect on the adenosine-induced hyperemia (2.10±0.34 mL · min-1 · g-1, P=NS). In the presence of L-NAME, however, when the adenosine response was attenuated, phentolamine was able to increase hyperemic perfusion (2.05±0.44 mL · min-1 · g-1, P<0.05). Conclusions - Inhibition of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. α-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.