Prostanoids and reactive oxygen species: team players in endothelium-dependent contractions.
The endothelial cells control the tone of the underlying vascular smooth muscle by releasing vasoactive substances. Endothelium-derived relaxing factors (EDRF), in particular nitric oxide have received considerable attention, but much less is known about the ability of the endothelial cells to release endothelium-derived contracting factors (EDCF). The possible players of endothelium-dependent contractions and the underlying mechanisms leading to the release of EDCF will be discussed in the present review. EDCF is likely to consist of two components: 1) prostanoids (including endoperoxides, prostacyclin, thromboxane A(2), and prostaglandin E(2)) and 2) reactive oxygen species. The former directly activate thromboxane/prostaglandin endoperoxide (TP) receptors of the vascular smooth muscle cells which leads to their contraction, while the latter first stimulate the cyclooxygenase in the smooth muscle with subsequent stimulation of the TP receptors by the prostanoids produced. Dysfunction in calcium handling is the leading causal factor for the exacerbated occurrence of endothelium-dependent contractions in the aorta of the spontaneously hypertensive rat (SHR). The observed increased expressions of endothelial COX-1, prostacyclin synthase, thromboxane synthase and enhanced TP receptor sensitivity are not prerequisites for, but intensify the magnitude of endothelium-dependent contractions. Selective TP receptor antagonists are effective in preventing endothelium-dependent contractions in vitro which highlights the prospective use of such drugs in correcting the imbalanced release of endothelium-derived vasoactive substances that accompany vascular disease.
Tang
Eva H C
EH
Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, China.
Vanhoutte
Paul M
PM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D045462:Endothelium-Dependent Relaxing Factors / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000502:physiology
D045462:Endothelium-Dependent Relaxing Factors; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D011982:Receptors, Prostaglandin; D000109:Acetylcholine; D002118:Calcium