Endothelium‐dependent contractions: when a good guy turns bad!

Abstract

Endothelial cells can induce contractions of the underlying vascular smooth muscle by generating vasoconstrictor prostanoids (endothelium-dependent contracting factor; EDCF). The endothelial COX-1 isoform of cyclooxygenase appears to play the dominant role in the phenomenon. Its activation requires an increase in intracellular Ca 2+ concentration. The production of EDCF is inhibited acutely and chronically by nitric oxide (NO), and possibly by endothelium-dependent hyperpolarizing factor (EDHF). The main prostanoids involved in endothelium-dependent contractions appear to be endoperoxides (PGH 2 ) and prostacyclin, which activate thromboxane-prostanoid (TP) receptors of the vascular smooth muscle cells. Oxygen-derived free radicals can facilitate the production and/or the action of EDCF. Endothelium-dependent contractions are exacerbated by ageing, obesity, hypertension and diabetes, and thus are likely to contribute to the endothelial dysfunction observed in older people and in essential hypertensive patients.

Cyclooxygenase-2-Derived Prostaglandin F 2α

“…In contrast to this, COX-1 is the main regulated enzyme in the rat aorta, 19 in which many studies on the identity of EDCF were performed. 1 Thus, the prostanoid synthetic pathways in humans appear to be closer to the hamster than the rat, as also suggested by the authors.…”

“…In a recent review by the same group, the contribution of PGF 2␣ to endothelium-dependent contraction has been considered marginal. 1 On the other hand, there might be situations, such as senescence, in which metabolic enzymes may become insufficient to degrade efficiently released PGs in conditions of elevated biosynthesis, including PGH 2 , thromboxane A 2 , and PGF 2␣ . 21 Because of the rapid hydrolysis of thromboxane A 2 into the inactive thromboxane B 2 and the (spontaneous) conversion of PGH 2 into PGF 2␣ , PGF 2␣ may locally accumulate and cause vasoconstriction.…”

“…The endothelium also produces contractile factors (EDCF) of different origin. 1 Thus, any reduced endothelium-dependent relaxation or even vasoconstriction could result from either loss of EDRFs, (enhanced) generation of EDCFs, or a combination of both. EDCFmediated vasoconstriction might prevail with increasing age, as well as disturbed endothelial function, for example, in hypertension 1,2 or type 2 diabetes.…”

“…1 One reason for this is the upregulation of endothelial COXs and enzymes of PG-endoperoxide catabolism during the aging process and hypertension with enhanced generation of these compounds 6,7 ; another reason is the low selectivity of prostanoids for their membrane receptors. Vasoconstrictor prostanoids act on vascular smooth muscle cells via the thromboxane-prostanoid (TP) receptor.…”

11,12-Epoxyeicosatrienoic acid induces vasodilator response in the rat perfused mesenteric vasculature

“…It is reported that an increase in the release of EDCF can lead to abnormal function of the endothelium and that occurs in different various vascular disorders. A variety of stimuli can cause EDCF production, including agonists like acetylcholine, adenosine nucleotides or by stretch 25. Inflow of calcium ions into the cells of the endothelium would occur in response to the different triggering elements.…”