title: Interaction of endothelial autacoids in microvascular control.
abstract: The endothelium releases dilating autacoids, such as nitric oxide (NO), prostaglandins, and endothelium-derived hyperpolarizing factor (EDHF). Different mechanisms of interaction between these autacoids have been identified and are briefly reviewed here. NO, which dilates resistance vessels via the second messenger cGMP, also amplifies the responses to vasodilators, which act by elevation of cAMP (e.g., prostaglandins), in a synergistic manner. This amplification is most likely due to a cGMP-dependent inhibition of the breakdown of cAMP. An interaction of these autacoids can not only be found in vascular smooth muscle cells but also in the endothelium. A closer look towards the site of production reveals that prostacyclin attenuates the release of NO, which is achieved by a decrease of the intracellular calcium levels in endothelial cells. This feedback mechanism leads to enhanced NO formation after inhibition of cyclooxygenase. While NO does not seem to modulate prostaglandin synthesis, it has been shown recently in coronary arteries that NO attenuates the release of EDHF. Under conditions of compromised NO formation EDHF might act via this mechanism as a second line of defense. This could help in maintaining endothelium-dependent vasodilation unless an altered smooth muscle responsiveness generally reduces the efficacy of endothelial vasodilators (including EDHF). Convincing experimental evidence for such an impaired relaxation of smooth muscle has been presented recently following exposure to elevated oxLDL levels.
authors.affiliation: Physiologisches Institut, Ludwig-Maximilians-Universität, Schillerstr. 44, 80336 München, Germany. dewit@lrz.uni-muenchen.de
authors.forename: C
authors.initials: C
authors.lastname: de Wit
authors.forename: S S
authors.initials: SS
authors.lastname: Bolz
authors.forename: U
authors.initials: U
authors.lastname: Pohl
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D012898:Autacoids / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D011464:Epoprostenol / Q000502:physiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D012898:Autacoids; D002317:Cardiovascular Agents; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D011464:Epoprostenol; D007213:Indomethacin