Paracrine functions of the coronary vascular endothelium.
Coronary vascular endothelial cells control vascular tone by modulating the local concentration of circulating vasoactive substances (e.g. adenine nucleotides, biogenic amines and bradykinin) and by synthesising and releasing the vasoactive autacoids nitric oxide (NO) and prostacyclin (PGI2). The fluid shear stress exerted by the streaming blood is the physiologically most important stimulus for a continuous endothelial 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 tissue. At the transcriptional level endothelium-derived NO modulates the regulation of a number of genes (e.g. monocyte chemoattractant protein-1, P-selectin and vascular cell adhesion molecule-1) most probably by direct and/or indirect interaction with transcription factors. In addition to NO and PGI2, the coronary vascular endothelium is also able to release a factor which causes hyperpolarisation of the underlying smooth muscle. This so-called endothelium-derived hyperpolarising factor (EDHF) displays the characteristics of a cytochrome P450-derived arachidonic acid metabolite. However, since NO is able to attenuate production of this factor, EDHF may contribute to the regulation of vascular tone essentially in situations associated with an apparent dysfunction of the endothelium.
Fleming
I
I
Zentrum der Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt/Main, Germany.
Bauersachs
J
J
Busse
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000502:physiology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D001679:Biogenic Amines / Q000502:physiology; D001685:Biological Factors / Q000502:physiology*; D001920:Bradykinin / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D011464:Epoprostenol / Q000096:biosynthesis / Q000502:physiology; D005246:Feedback; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials; D009129:Muscle Tonus; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019007:P-Selectin / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism
D000227:Adenine Nucleotides; D001095:Arachidonic Acids; D001679:Biogenic Amines; D001685:Biological Factors; D019007:P-Selectin; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases; D000109:Acetylcholine; D001920:Bradykinin