Shear Stress Determine the Basal Release of Endothelium-Derived Relaxing Factor in the Intact Rabbit Coronary Vascular Bed

We investigated the mechanisms that are responsible for the basal release of endotheliumderived relaxing factor (EDRF), which is likely to be identical with nitric oxide, in the intact coronary circulation. The increase in cGMP content of platelets passing through the coronary bed of the isolated rabbit heart was used as an index of EDRF release. Platelet cGMP content after passage through the heart under control conditions (flow rate of 20 ml/min) amounted to 0.50±0.10 pmol/mg protein. Inhibition of endothelial nitric oxide synthesis by 30 ,uM NG-nitro-L-arginine (L-NNA) reduced this amount by more than 60%. Increasing flow rate from 20 ml/min to 40 and 60 ml/min led to flow-dependent dilation as reflected by the subsequent drop in perfusion pressure after an initial rise. The flow-dependent dilation was associated with