Endothelium-derived Hyperpolarizing Factor and Endothelium-dependent Relaxations

Abstract

The endothelial cells inhibit the tone of the underlying vascular smooth muscle by releasing endothelium-derived relaxing factors (EDRF). The existence of at least two such factors, nitric oxide and endothelium-derived hyperpolarizing factor (EDHF), has been demonstrated. EDHF is an as yet unidentified substance that hyperpolarizes vascular smooth muscle cells and causes their relaxation. The contribution of endothelium-dependent hyperpolarization varies along the vascular tree. Particularly in smaller blood vessels, EDHF acts on vascular smooth muscle in cooperation with nitric oxide. Basal release of EDHF is not likely to occur, at least in vitro. The production and/or release of EDHF is regulated by the cytosolic concentration of Ca2+ ions, derived both from the extracellular space and intracellular stores. Calmodulin may be involved in its production and/or release. EDHF hyperpolarizes the vascular smooth muscle by opening K+ channels. The hyperpolarization closes voltage-dependent Ca2+ channels and, as a consequence, EDHF relaxes blood vessels. In the absence of chemical identification of EDHF, it is difficult to assess its contribution to endothelium-dependent relaxations in vivo.

Vasodilatory Effect of Basic Fibroblast Growth Factor in Isolated Rat Cerebral Arterioles: Mechanisms Involving Nitric Oxide and Membrane Hyperpolarization.

“…Recent studies have shown that EDNO-dependent vasodilators, such as bradykinin and acetylcholine, hyperpolarize the membrane of SMCs in rabbit cerebral arteries and guinea-pig arteries. 3,17) However, the nature of the mediating factor causing the hyperpolarization is controversial. 17) A number of previous studies 4,17) have suggested the possible involvement of EDHF (yet to be identified), which is distinct from EDNO since NO synthase blockers and NO do not change MP.…”

“…3,17) However, the nature of the mediating factor causing the hyperpolarization is controversial. 17) A number of previous studies 4,17) have suggested the possible involvement of EDHF (yet to be identified), which is distinct from EDNO since NO synthase blockers and NO do not change MP. More recently, EDHF was suggested to be a cytochrome P450-derived arachidonic acid metabolite.…”

“…5) Electrophysiological studies have revealed that membrane hyperpolarization of SMCs, which is likely to be mediated by endothelium-derived hyperpolarizing factor (EDHF), is associated with EDNO-dependent vasodilation. 17) A possible explanation for this phenomenon is that an increase in the endothelial cytosolic concentration of Ca 2＋ ions in response to agonists triggers both EDHF and EDNO release. 17) bFGF increases intracellular Ca 2＋ , 18) possibly by binding to a tyrosine kinase receptor.…”

“…17) A possible explanation for this phenomenon is that an increase in the endothelial cytosolic concentration of Ca 2＋ ions in response to agonists triggers both EDHF and EDNO release. 17) bFGF increases intracellular Ca 2＋ , 18) possibly by binding to a tyrosine kinase receptor. 2) This study investigated whether bFGF simultane-Y.…”

Coronary artery blood how: Physiologic and pathophysiologic regulation

“…Hyperpolarization also causes deactivation of cellular voltage-gated calcium channels, a reduction in calcium entry into muscle cells, and therefore vascular smooth muscle relaxation. 38 Prostacyclin, a product of the arachidonic acid cascade, is also released from the coronary artery endothelium due to stimulation by thrombin, bradykinin, histamine, adenine nucleotides (ATP and ADP), and thromboxane A z .~~ In contrast to NO, which causes vasorelaxation through increases in cGMP, prostacyclin produces vascular smooth muscle relaxation through increases in intracellular cyclic adenosine monophosphate M CAMP)?^ Cyclic AMP facilitates calcium uptake by the sarcoplasmic reticulum in vascular smooth muscle as well as calcium extrusion from the cell to the extracellular space, thereby producing vascular smooth muscle…”