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The alpha adrenoceptors on endothelial cells.
Federation Proceedings
|August 1, 1986
Summary
Endothelial cells release endothelium-derived relaxing factor (EDRF) that influences vascular smooth muscle contraction. The endothelium
Area of Science:
- Vascular pharmacology
- Endothelial function
- Adrenoceptor signaling
Background:
- Endothelial cells produce endothelium-derived relaxing factor (EDRF), a key mediator of vasodilation.
- Norepinephrine (NE) is a potent vasoconstrictor, but its effects can be modulated by endothelial factors.
- Alpha-adrenoceptors are involved in regulating vascular tone.
Purpose of the Study:
- To investigate the role of the endothelium in mediating vascular responses to norepinephrine (NE).
- To characterize the specific adrenoceptors involved in NE-mediated relaxation and contraction.
- To compare endothelial and smooth muscle adrenoceptor distribution across different species and vascular beds.
Main Methods:
- In vitro isometric tension studies on isolated coronary artery rings from greyhound, mongrel dog, and pig.
- Experiments involved pre-treatment with propranolol to block beta-adrenoceptors.
- Assessment of NE-induced contractions and relaxations with and without intact endothelium, and in the presence of various alpha-adrenoceptor antagonists (phentolamine, idazoxan, yohimbine, prazosin).
Main Results:
- Removal of the endothelium enhanced NE-induced contractions in coronary arteries.
- NE induced relaxation in pre-contracted pig coronary arteries only when the endothelium was present, an effect antagonized by alpha-2 adrenoceptor blockers, suggesting EDRF release.
- Relaxation to NE in dog coronary arteries required prazosin (alpha-1 antagonist), indicating alpha-1 stimulation on smooth muscle can override EDRF effects.
Conclusions:
- Endothelium-derived relaxing factor (EDRF) plays a significant role in modulating vascular responses to norepinephrine.
- Alpha-2 adrenoceptors on endothelial cells mediate EDRF release, while alpha-1 and alpha-2 adrenoceptors on vascular smooth muscle influence contraction.
- The distribution and function of these adrenoceptors vary across species and vascular beds, highlighting the importance of considering endothelial integrity in interpreting vascular pharmacology.