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Endothelium-dependent contractions: when a good guy turns bad!
Paul M Vanhoutte1, Eva H C Tang
1Department of Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China. vanhoutt@hkucc.hku.hk
The Journal of Physiology
|September 27, 2008
Summary
Endothelial cells generate vasoconstrictor prostanoids (EDCF) that contract vascular smooth muscle, primarily via the COX-1 enzyme. Nitric oxide (NO) inhibits EDCF production, impacting conditions like hypertension.
Area of Science:
- Vascular biology
- Endothelial function
- Prostanoid signaling
Background:
- Endothelial cells regulate vascular tone by producing endothelium-dependent contracting factors (EDCF).
- The cyclooxygenase-1 (COX-1) isoform is key in EDCF generation, requiring intracellular calcium increase.
- Nitric oxide (NO) and endothelium-dependent hyperpolarizing factor (EDHF) can inhibit EDCF production.
Purpose of the Study:
- To elucidate the mechanisms and signaling pathways of endothelium-dependent contractions.
- To identify the specific prostanoids and receptors involved in EDCF-mediated vasoconstriction.
- To understand the role of EDCF in endothelial dysfunction associated with aging and hypertension.
Main Methods:
- Investigated the role of endothelial COX-1 in EDCF production.
- Examined the influence of intracellular Ca(2+) on EDCF generation.
- Assessed the inhibitory effects of NO and EDHF on EDCF.
- Identified prostanoids (PGH(2), prostacyclin) and TP receptor activation.
- Studied the impact of free radicals on EDCF action.
Main Results:
- Endothelial COX-1 is dominant in generating EDCF.
- EDCF production is calcium-dependent.
- Nitric oxide (NO) acutely and chronically inhibits EDCF.
- Endoperoxides (PGH(2)) and prostacyclin acting on TP receptors mediate contractions.
- Oxygen-derived free radicals can enhance EDCF production/action.
Conclusions:
- EDCF, mediated by COX-1, PGH(2), prostacyclin, and TP receptors, contributes to vascular smooth muscle contraction.
- NO and EDHF act as endogenous inhibitors of EDCF.
- Impaired EDCF regulation is linked to endothelial dysfunction in aging, obesity, hypertension, and diabetes.
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