Endothelium-dependent hyperpolarizations: past beliefs and present facts

Ann Med. 2007;39(7):495-516. doi: 10.1080/07853890701491000.

Abstract

Endothelium-dependent relaxations are attributed to the release of various factors, such as nitric oxide, carbon monoxide, reactive oxygen species, adenosine, peptides and arachidonic acid metabolites derived from the cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases pathways. The hyperpolarization of the smooth muscle cell can contribute to or be an integral part of the mechanisms underlying the relaxations elicited by virtually all these endothelial mediators. These endothelium-derived factors can activate different families of K(+) channels of the vascular smooth muscle. Other events associated with the hyperpolarization of both the endothelial and the vascular smooth muscle cells (endothelium-derived hyperpolarizing factor (EDHF)-mediated responses) contribute also to endothelium-dependent relaxations. These responses involve an increase in the intracellular Ca(2+) concentration of the endothelial cells followed by the opening of Ca(2+)-activated K(+) channels of small and intermediate conductance and the subsequent hyperpolarization of these cells. Then, the endothelium-dependent hyperpolarization of the underlying smooth muscle cells can be evoked by direct electrical coupling through myoendothelial junctions and/or the accumulation of K(+) ions in the intercellular space between the two cell types. These various mechanisms are not necessarily mutually exclusive and, depending on the vascular bed and the experimental conditions, can occur simultaneously or sequentially, or also may act synergistically.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Polarity / physiology*
  • Coronary Artery Disease / etiology*
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / pathology*
  • Endothelium, Vascular / physiopathology
  • Humans
  • Myocytes, Smooth Muscle / physiology*
  • Vasoconstriction / physiology
  • Vasodilation / physiology