The endothelium can secrete both relaxing and contracting substances. One of the most powerful stimuli to the release of the former are thrombin and aggregating platelets. This contributes to the protective role of the endothelium against inappropriate intraluminal platelet aggregation and coagulation in blood vessels with an intact intima. Thrombin-induced, endothelium-dependent relaxations have been obtained in isolated arteries of different species, including humans. Endothelium-dependent relaxations can be evoked by autologous platelets in isolated blood vessels of the dog, pig and rat; they can be obtained in canine coronary arteries with human platelets. The major platelet-products involved in these endothelium-dependent relaxations are 5-hydroxytryptamine (serotonin) and the adenine nucleotides. Although platelet-activating factor (PAF) can evoke endothelium-dependent relaxation it only does so at concentrations much higher than those occurring under physiological conditions; since the relaxations are not prevented by PAF-antagonists, they are non-specific in nature.The receptor mediating the endothelium-dependent relaxations to serotonin released from the aggregating platelets can be subtyped as a S1~(5HT1) serotonergic receptor;those mediating the response to the adenine nucleotides as P2y-purinergic receptors. In the absence of the endothelium aggregating platelets cause contractions of vascular smooth muscle; these are mediated by a mixture of S1-like and S2~serotoner-gic receptors in coronary arteriesof the dog, and by S2-serotonergic receptors in those of the pig. Thus, in the porcine coronary artery, the S2-serotonergic antagonist ketanserin markedly enhances the platelet-induced endothelium-dependent relaxation. After previous (four weeks) injury, the regenerated endothelium of the porcine coronary artery loses the ability to respond to serotonin,and is unable to prevent the constrictionsevoked by aggregating platelets. The endothelium-dependent relaxations of porcine coronary arteries evoked by aggregating platelets are potentiated by chronic treatmentof the donor animals with cod liver oil. These studies emphasize the protective roleof the endothelial cells against the vasoconstriction (vasospasm) induced by aggregating platelets. This role is depressed after previous injury, and can be facilitatedby dietary adj ustments.
Cyclopiazonic acid induces cytosolic Ca2+ elevation in endothelial cells and endothelium-dependent relaxation of the porcine coronary artery.
