Eicosanoid production by the coronary microvascular endothelium.
Cultured rabbit coronary microvessel endothelial (RCME) cells have been used as an in vitro model to study the regulation of microvascular endothelial cell prostaglandin (PG) production by hormones, vasoactive drugs, and inflammatory mediators in an environment that can be tightly controlled and that is unaffected by interactions with other cell types, physical stimulation, or alterations in oxygenation. The most potent stimuli for RCME cell PG secretion were substances associated with inflammation, including histamine, interleukin 1, leukotriene D4, fMet-Leu-Phe, interferon-gamma, and exogenous phospholipases. Inhibition of calcium availability by lower [Ca2+]o or by treatment with calcium channel blockers reduced A23187-stimulated PG release but increased PG synthesis from exogenous arachidonic acid (AA). These observations suggest that Ca2+ may regulate several steps in the pathway leading to PG synthesis and release. Elevated intracellular [Ca2+] may, on the one hand, promote PG production by stimulating phospholipase A2 leading to AA release and, on the other hand, limit the magnitude of the response by increasing the rate of AA reacylation. Glucocorticoids reduce PG production by RCME cells via an action that requires new protein and mRNA synthesis and appears to involve the production of an endothelial cell-derived phospholipase inhibitory protein, or "endocortin." Thus, microvascular endothelial cells can both contribute to (by the release of PGs and possibly platelet-activating factor-acether) and limit (by the production of endocortins) the degree of a local inflammatory response in the heart.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D002395:Catecholamines / Q000494:pharmacology; D003331:Coronary Vessels / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D015232:Dinoprostone; D004285:Dogs; D004727:Endothelium / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D008833:Microcirculation; D011453:Prostaglandins / Q000096:biosynthesis* / Q000378:metabolism; D011458:Prostaglandins E / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects
D001095:Arachidonic Acids; D002395:Catecholamines; D011453:Prostaglandins; D011458:Prostaglandins E; D016718:Arachidonic Acid; D011464:Epoprostenol; D015232:Dinoprostone; D002118:Calcium