Prostacyclin-mediated compensatory mechanism in the coronary circulation during acute NO synthase blockade

Nitric oxide (NO) in contrast to most prostanoids, plays a major role in the maintenance of coronary arterial tone under physiological conditions. However, in case of endothelial damage or other NO-depleting situations the importance of other vasodilating mechanisms may be increased. The aim of the present study was to investigate the crosstalk between the L-arginine - NO and the prostanoid systems in isolated rat hearts. Coronary flow and cardiac dynamics were measured in a standard Langendorff perfusion system. Application of indomethacin in the perfusion media failed to change coronary flow. Administration of L-NA, however, significantly decreased coronary flow by 24.8 +/- 2.3% (p < 0.01 vs. untreated control). In the presence of indomethacin, L-NA decreased coronary flow to an even greater extent by 35.8 +/- 5.2% (p < 0.05 vs. L-NA alone). Treatment of the preparations with L-NA or indomethacin failed to change cardiac work, coapplication of both drugs together, however, decreased cardiac work by 45 +/- 11% (p < 0.05 vs. untreated control). Heart rate remained constant throughout the experimental period and did not differ significantly between the treatment groups. The prostacyclin content of the effluent from the L-NA treated hearts was significantly higher than that of controls. We conclude that in case of decreased NO levels in the coronary circulation, arterial tone is maintained by prostacyclin production.