The endothelium-derived hyperpolarizing factor: does it play a role in vivo and is it involved in the regulation of vascular tone only?
Several investigations performed in vitro have shown that vascular endothelia can release diffusible compounds capable of inducing hyperpolarization of the smooth muscle fibers. Experiments in vitro have shown that these compounds can cause coronary vasodilation and alter cardiac performance. Experiments in vivo only showed the occurrence of vasodilation. While it has been shown that the release of these endothelium-derived hyperpolarizing factors (EDHFs) is not impaired by the inhibition of nitric oxide synthase and cyclooxygenase, the precise nature of the compound(s) has not yet been identified. It is possible that they vary depending on the organ and animal species. However, a common feature of the activity of EDHFs is the activation of calcium-dependent potassium channels, inhibitable by charybdotoxin and apamin. Furthermore in the coronary circulation of many species EDHF seems to be a cytochrome P450-dependent non-prostanoid metabolite of arachidonic acid activated by a number of chemical and physical stimuli similar to those which are known to activate endothelial nitric oxide synthase. Using compounds which inhibit cytochrome P450 and blockers of the calcium-dependent potassium channels, researchers can study the physiological and pathophysiological relevance of EDHF in vivo thus disclosing the potential therapeutic applications of the basic knowledge in this field.
Pagliaro
P
P
Department of Clinical and Biological Sciences, University of Turin, Italy. pasquale.pagliaro@unito.it
Rastaldo
R
R
Paolocci
N
N
Gattullo
D
D
Losano
G
G
D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D002118:Calcium / Q000494:pharmacology; D003331:Coronary Vessels / Q000502:physiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D015221:Potassium Channels; C067410:endothelium-dependent hyperpolarization factor; D003577:Cytochrome P-450 Enzyme System; D002118:Calcium