TY - JOUR

T1 - Influence of nitric oxide synthase and adrenergic inhibition on adenosine-induced myocardial hyperemia

AU - Buus, Niels H.

AU - Bøttcher, Morten

AU - Hermansen, Flemming

AU - Sander, Mikael

AU - Nielsen, Torsten T.

AU - Mulvany, Michael J.

PY - 2001

Y1 - 2001

N2 - 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 alpha-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. alpha-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.

AB - 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 alpha-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. alpha-Adrenergic blockade has no effect on adenosine-induced hyperemia unless NO synthesis is inhibited.

KW - Adenosine

KW - Nitric oxide

KW - Perfusion

KW - Receptors, adrenergic, alpha

KW - Vasodilation

UR - http://www.scopus.com/inward/record.url?scp=0035818565&partnerID=8YFLogxK

U2 - 10.1161/hc4401.098293

DO - 10.1161/hc4401.098293

M3 - Journal article

C2 - 11696470

VL - 104

SP - 2305

EP - 2310

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 19

ER -