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

[摘要] 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 Results-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 N-G-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 a-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 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 increase hyperemic perfusion (2.05 +/-0.44 mL . min(-1) . g(-1), P <0.05). Conclusions-Inhibit ion of endogenous NO synthesis attenuates myocardial perfusion during adenosine-induced hyperemia, indicating that coronary vasodilation by adenosine is partly endothelium dependent. alpha -Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.

[关键词] CORONARY FLOW RESERVE;BLOOD-FLOW;YOUNG MEN;ARTERIAL-PRESSURE;N-13 AMMONIA;HEART-RATE;HUMANS;VASODILATION;HYPERTENSION;MICROCIRCULATION