ENDOTHELIUM-DERIVED RELAXING FACTOR PARTICIPATES IN THE TRANSMURAL DISTRIBUTION OF CORONARY BLOODFLOW

OBJECTIVE: To study the role of endothelium-derived relaxing factor (E DRF) - which participates in the regulation of coronary vascular tone, but has an unknown role in the transmural distribution of coronary fl ow - in transmural coronary flow distribution during steady basal flow and during reactive hyperemia in the left ventricular wall of the dog . DESIGN: Sixteen mongrel dogs of either sex weighing between 14 and 2 4 kg were anesthetized with sodium pentobarbital. The lungs were mecha nically ventilated and the thoraces were opened. Circumflex coronary f low was measured with an electromagnetic flowmeter, and its transmural distribution across four layers of the left ventricular wall was meas ured with radioactive microspheres. Measurements were done during stea dy basal flow and during peak reactive hyperemia before and after the inhibition of the EDRF synthesis with N-omega-nitro-L-arginine (NNLA). Mean aortic and systolic left ventricular pressures and heart rate we re kept constant, and left ventricular end-diastolic pressure increase d by only 3.3 mmHg during reactive hyperemia. MAIN RESULTS: NNLA produ ced a mean decrease of steady basal flow of 22.3+/-0.9% (P<0.01). Flow decreased in all layers of the wall; the decrease, however, was propo rtionally less in the subendocardium (P<0.05). During reactive hyperem ia (before NNLA), flow was redistributed to the subendocardium (compar ed with steady basal flow). Administration of NNLA reduced the magnitu de of peak reactive flow to all layers in the wall, showing a relative enhancement of flow in the subendocardium. CONCLUSIONS: These results suggest that the EDRF participates in the regulation of coronary bloo dflow and its distribution across the left ventricular wall.