Circulation, Vol 88, 43-54, Copyright © 1993 by American Heart Association
DC Lefroy, T Crake, NG Uren, GJ Davies and A Maseri
BACKGROUND. NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of
nitric oxide synthesis, was used to determine the effects of inhibition of
nitric oxide synthesis in the human coronary circulation. METHODS AND
RESULTS. Twelve patients (mean age, 52 +/- 2 years) with normal epicardial
coronary arteries were studied. The surface ECG, systemic blood pressure,
and coronary venous oxygen saturation (coronary SvO2), an index of coronary
blood flow, were monitored continuously. Coronary artery diameter was
measured by quantitative arteriography. L-NMMA was given as intracoronary
infusions at 2 mL/min via the diagnostic arteriography catheter. In two
patients, low doses (0.01 to 5 mumol/min) of L-NMMA were infused into the
nondominant right coronary artery. There was no evidence of ischemia in
these patients, who were not included in the final analysis. In 10
patients, higher doses of L- NMMA (4, 10, and 25 mumol/min, each for 5
minutes) were infused into the left coronary artery. In six patients,
incremental doses of acetylcholine were infused (1, 10, and 100 nmol/min,
each for 3 minutes) before and after the L-NMMA infusion. Finally, in all
patients, sodium nitroprusside, a nitric oxide donor, was infused. No
patient developed myocardial ischemia. The heart rate and systemic blood
pressure remained unchanged throughout the infusions. L-NMMA (25
mumol/min), compared with the control saline infusion, caused a significant
reduction in distal (-5.9 +/- 2.1%, P = 0.021) but not proximal left
anterior descending coronary artery (LAD) diameter and a fall in coronary
SvO2 from 37.5 +/- 2.8% to 34.3 +/- 2.8% (P = 0.019). Sodium nitroprusside
dilated the proximal (17.8 +/- 6.9%, P = 0.033) and distal (24.5 +/- 6.5%,
P = 0.006) LAD and increased the coronary SvO2 to 61.6 +/- 5.0% (P =
0.0002). Acetylcholine caused significant dilatation of the distal (13.8
+/- 5.4%, P = 0.049) but not proximal LAD and a significant increase in
coronary SvO2 from 36.5 +/- 3.5% to 59.2 +/- 2.8% (P < 0.0001). After
L-NMMA, acetylcholine-induced dilatation of the distal LAD was abolished,
but the rise in coronary SvO2 was unchanged. CONCLUSIONS. Inhibition of
nitric oxide synthesis in the human coronary circulation caused a decrease
in basal distal LAD diameter and basal coronary blood flow assessed by
coronary SvO2, indicating that there is a small basal release of nitric
oxide in the distal epicardial coronary arteries and resistive vessels.
Distal epicardial coronary artery dilatation in response to acetylcholine
is nitric oxide dependent, but coronary resistive vessel dilatation is not.
ARTICLES
Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans
Department of Medicine (Cardiology), Hammersmith Hospital, London, UK.
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