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

Background-Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific inv estigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothe lial NO production or is influenced by adrenergic mechanisms. Methods and Results-In 12 healthy men, myocardial perfusion was measured wi th 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 N-G-nitro-L-arginine methyl ester (L-NAME, 4 mg/kg) was infused, and perfusion during adenosine-induced hyperemia was de termined. Last, in both protocols, the a-receptor blocker phentolamine was infused, and perfusion during adenosine-induced hyperemia was determined ag ain. 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 pre ssure 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 add ition of phentolantine 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 incre ase hyperemic perfusion (2.05 +/-0.44 mL . min(-1) . g(-1), P <0.05). Conclusions-Inhibit ion of endogenous NO synthesis attenuates myocardial pe rfusion during adenosine-induced hyperemia, indicating that coronary vasodi lation by adenosine is partly endothelium dependent. alpha -Adrenergic bloc kade has no effect on adenosine-induced hyperemia unless NO synthesis is in hibited.