Impact of coronary risk factors on contribution of nitric oxide and adenosine to metabolic coronary vasodilation in humans.
OBJECTIVE
The contribution of nitric oxide (NO) and adenosine to the increase in coronary blood flow (CBF) induced by cardiac pacing was investigated in 28 subjects with angiographically normal coronary arteries with and without one or more risk factors for atherosclerosis.


BACKGROUND
NO and adenosine are important in the regulation of coronary circulation, and the inhibition of NO synthesis increases adenosine production during cardiac pacing in experimental models.


METHODS
Coronary artery diameters and CBF were assessed by quantitative coronary arteriography and Doppler flow velocity measurement. Plasma levels of nitrites and nitrates (NOx) (stable end products of NO), adenosine and lactate were measured, and blood gas analysis was performed.


RESULTS
The extent of CBF response to cardiac pacing did not differ between the 14 subjects with and the 8 subjects without risk factors for atherosclerosis. NOx (12.0+/-0.9 vs. 14.9+/-1.1 ,amol/liter [mean+/-SD], p < 0.05), but not adenosine (50.8+/-7.2 vs. 50.8+/-6.5 nmol/liter), levels in coronary sinus blood increased in the subjects without risk factors. In contrast, adenosine (58.9+/-7.5 vs. 77.4+/-9.8 nmol/liter, p < 0.05), but not NOx (11.1+/-1.1 vs. 12.2+/-1.1 micromol/liter), levels increased in subjects with risk factors. Aminophylline, an antagonist of adenosine receptors, blunted CBF response to cardiac pacing in six subjects with risk factors. The number of risk factors showed a negative correlation (p < 0.05) with NOx production and a positive correlation (p < 0.05) with adenosine production during cardiac pacing, respectively.


CONCLUSIONS
NO and adenosine are increased during metabolic coronary vasodilation induced by cardiac pacing. Adenosine production may be a compensatory mechanism when NO production is reduced.
Minamino
T
T
First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
Kitakaze
M
M
Matsumura
Y
Y
Nishida
K
K
Kato
Y
Y
Hashimura
K
K
Matsu-Ura
Y
Y
Funaya
H
H
Sato
H
H
Kuzuya
T
T
Hori
M
M
D000241:Adenosine / Q000502:physiology*; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity; D002304:Cardiac Pacing, Artificial; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000453:epidemiology; D003326:Coronary Circulation / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D012307:Risk Factors; D014664:Vasodilation / Q000502:physiology*
D009569:Nitric Oxide; D000241:Adenosine