ROLE OF BASAL RELEASE OF NITRIC-OXIDE ON CORONARY FLOW AND MECHANICAL PERFORMANCE OF THE ISOLATED RAT-HEART

1. The role of nitric oxide (NO) in the regulation of coronary flow and mechanical function was studied in isolated working rat hearts. 2. The inhibition of basal release of NO by L-N(g)-monomethylarginine (L-NMMA; 500 muM), a specific inhibitor of its synthesis, induced a reduction of coronary flow to 39.1% (+/- 3.4) of its basal level. 3. Associated with this was a drop of cardiac output to 58.10% (+/- 5.42) of control values. 4. This mechanical dysfunction, which was more pronounced in hypertrophied hearts, appears to be related to ischaemia, as it was prevented by simultaneously administered glyceryl trinitrate. Furthermore, L-NMMA did not alter the contractile activity of isolated cardiac myocytes, thereby excluding a direct toxic effect. 5. These findings provide evidence that NO plays a crucial role in the maintenance of basal coronary flow and appears to be essential for sustaining mechanical activity.