Endothelium derived relaxant factors (EDRFs)<\/p>\n
Endothelium derived relaxant factor is produced and released by the endothelium to\u00a0cause smooth muscle relaxation. The characterized EDRFs include nitric oxide (NO),\u00a0prostacyclin (PGI2<\/sub>), and endothelium-derived hyperpolarization factor (EDHF). By\u00a0acting on endothelial membrane receptors, neurohumoral substances and shear stress cause a G-protein-mediated increase in calcium influx by opening non-selective\u00a0cation channels. Increase in calcium influx hydrolyzes phosphotidyl inositol 4,5-\u00a0bisphosphate (PIP2) yielding inositol triphosphate (IP3<\/sub>), which causes calcium efflux\u00a0from intracellular stores. Thus, calcium enters cytosol, which\u00a0activates the production of EDRFs.<\/p>\n Nitric oxide (NO) Prostacyclin (PGI2<\/sub>) Endothelium-derived hyperpolarizating factors (EDHFs)
\nNO is mainly found in coronary, pulmonary and cerebral arteries.\u00a0NO is synthesized from L-arginine by endothelial isoform of NO synthase (eNOS)\u00a0which is activated by Ca2+<\/sup>-calmodulin. Endothelial NO reaches vascular smooth\u00a0muscle cell by diffusing across the endothelial cell membrane and activates soluble\u00a0guanylate cyclase (sGC) to form cyclic GMP (cGMP) in the smooth muscle cell. NO\u00a0has been found to induce relaxation by activating large-conductance Ca2+<\/sup>-activiated\u00a0K+<\/sup>\u00a0channels (BKCa<\/sub>) and ATP-sensitive K+ channels (KATP) in smooth muscle cells,\u00a0which suggest that NO hyperpolarize smooth muscle cells\u00a0directly and indirectly via activation of sGC.<\/p>\n
\nPGI2<\/sub>\u00a0is a metabolite of arachidonic acid by the action of cyclooxygenase enzyme<\/a>\u00a0(COX) in most blood vessels. Arachidonic acid is derived from membrane-bound\u00a0phospholipids by phospholipase A2 (PLA2<\/sub>). Then arachidonic acid is converted to\u00a0PGG2<\/sub>\u00a0by COX. PGG2 converts to PGH2<\/sub>\u00a0by hydroperoxidase. Consequently, PGH2<\/sub>\u00a0<\/sub>converted to vasoactive prostanoids such as protstacyclin (PGI2), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), prostaglandin F2\u03b1 (PGF2\u03b1) and thromboxane A2\u00a0(TXA2) by the action of various synthases. PGI2 induces relaxation of vascular\u00a0smooth muscle by activating IP receptor-coupled BKCa channel and IP receptors\u00a0coupled to adenylate cyclase (AC).<\/p>\n
\nEndothelial cell releases an endothelium-derived vasodilator which is resistant to\u00a0inhibitors of eNOS and COX enzyme. It causes relaxation by hyperpolarizing\u00a0vascular smooth muscle cell. Hyperpolarization in endothelial cells is triggered by an increased concentration of Ca2+<\/sup>, then the endothelial small-conductance (SKCa<\/sub>) and\u00a0intermediate-conductance (IKCa) Ca2+<\/sup>-activated K+<\/sup>\u00a0channels are activated, which\u00a0causes the efflux and accumulation of K+<\/sup>\u00a0<\/sup>in the myo-endothelial space. The\u00a0increased electrochemical gradient of Ca2+<\/sup>\u00a0enhances the influx of Ca2+<\/sup>\u00a0into the\u00a0hyperpolarized cell by voltage-independent Ca2+ channels, which enhances EDRF\u00a0synthesis, triggering EDHF-mediated responses in the endothelial cell. The possible\u00a0EDHFs candidates include epoxyeicosatrienoic acid, K+ ions and gap junction.<\/p>\n