Endothelium-derived relaxing factor participates in the transmural distribution of coronary bloodflow.

ABSTRACT

OBJECTIVE: To study the role of endothelium-derived relaxing factor (EDRF)--which participates in the regulation of coronary vascular tone, but has an unknown role in the transmural distribution of coronary flow--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 24 kg were anesthetized with sodium pentobarbital. The lungs were mechanically ventilated and the thoraces were opened. Circumflex coronary flow was measured with an electromagnetic flowmeter, and its transmural distribution across four layers of the left ventricular wall was measured with radioactive microspheres. Measurements were done during steady 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 were kept constant, and left ventricular end-diastolic pressure increased by only 3.3 mmHg during reactive hyperemia. MAIN RESULTS: NNLA produced 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 proportionally less in the subendocardium (P < 0.05). During reactive hyperemia (before NNLA), flow was redistributed to the subendocardium (compared with steady basal flow). Administration of NNLA reduced the magnitude 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 bloodflow and its distribution across the left ventricular wall.