Autonomic modulation of contractions to endothelin-1 in canine coronary arteries.
Endothelin-1 contracts vascular smooth muscle and inhibits release of neurotransmitter from adrenergic and cholinergic neurons. Experiments were designed to investigate the interaction of these mechanisms in a blood vessel that receives both adrenergic and cholinergic innervation. Rings cut from canine left anterior descending coronary arteries were suspended in organ chambers for the measurement of isometric force. In some rings, the endothelium was removed. Endothelin-1 caused concentration-dependent increases in tension in all rings. During electrical stimulation (1 Hz, 9 V, 2 msec), the contractions to endothelin-1 were reduced significantly. In rings without endothelium, this decrease was greater in the presence of atropine (10(-6) M) and was eliminated by a combination of phentolamine (10(-5) M) and propranolol (5 x 10(-6) M). Contractions to endothelin-1 during electrical stimulation in rings with endothelium were significantly less than those without endothelium. This difference was eliminated by atropine and NG-monomethyl L-arginine (10(-4) M). The presynaptic effects of endothelin-1 were studied by measurement of tritium-labeled norepinephrine. Phasic electrical stimulation induced release of norepinephrine; this was inhibited by endothelin-1 at high concentrations (4 x 10(-7) M) in the presence of atropine. These results suggest that the major effect of endothelin-1 is postsynaptic in canine coronary arteries. However, contractions to endothelin-1 may be modulated by the level of sympathetic and parasympathetic tone. In situations in which innervation to the coronary arteries is altered, for example, in hearts used for transplantation, the contractile effects of endothelin-1 would prevail.
Department of Surgery, Mayo Clinic and Foundation, Rochester, MN 55905.
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Aarnio
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McGregor
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Miller
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001341:Autonomic Nervous System / Q000502:physiology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D016232:Endothelins / Q000494:pharmacology*; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014661:Vasoconstriction
D016232:Endothelins; D011433:Propranolol; D009638:Norepinephrine; D010646:Phentolamine