PARACRINE FUNCTIONS OF THE CORONARY VASCULAR ENDOTHELIUM

Coronary vascular endothelial cells control vascular tone by modulatin g the local concentration of circulating vasoactive substances (e.g. a denine nucleotides, biogenic amines and bradykinin) and by synthesisin g and releasing the vasoactive autacoids nitric oxide (NO) and prostac yclin (PGI,). The fluid shear stress exerted by the streaming blood is the physiologically most important stimulus for a continuous endothel ial NO production, which counteracts neuro- and myogenic constriction. This shear stress-dependent NO release represents a highly effective local system for maintaining adequate blood flow to the myocardial tis sue. At the transcriptional level endothelium-derived NO modulates the regulation of a number of genes (e.g. monocyte chemoattractant protei n-1, P-selectin and vascular cell adhesion molecule-1) most probably b y direct and/or indirect interaction with transcription factors. In ad dition to NO and PGI(2), the coronary vascular endothelium is also abl e to release a factor which causes hyperpolarisation of the underlying smooth muscle. This so-called endothelium-derived hyperpolarising fac tor (EDHF) displays the characteristics of a cytochrome P450-derived a rachidonic acid metabolite. However, since NO is able to attenuate pro duction of this factor, EDHF may contribute to the regulation of vascu lar tone essentially in situations associated with an apparent dysfunc tion of the endothelium.