The endothelium inhibits activation by calcium of vascular neurotransmission.
The role of calcium in the inhibition by the endothelium of adrenergic neurotransmission was studied in isolated rabbit carotid artery. Contractions induced by transmural electrical field stimulation (0.5-8 Hz), norepinephrine (10(-8)-3 X 10(-5) M), potassium depolarization (15-30 mM), or by readdition of calcium (0.15-2.4 mM) to a calcium-free medium containing potassium (15 mM) were significantly smaller in rings with compared with rings without endothelium. The voltage-dependent calcium channel activator, BAY K 8644 (10(-6) M), increased contractions to all contractile stimuli in rings with more than in rings without endothelium and thereby abolished the inhibitory influence of the endothelium. The inhibition of neurogenic contractions by the endothelium was also, in part, prejunctional, as indicated by decreased overflow of endogenous norepinephrine from superfused segments with compared with segments without endothelium evoked by electrical stimulation (2 Hz) or by reinfusion of calcium (2.5 mM) to calcium-free medium containing potassium (80 mM). BAY K 8644 (10(-6) M) enhanced the overflow of norepinephrine evoked by electrical stimulation or calcium from segments with more than from segments without endothelium and abolished the difference. Thus the endothelium inhibits activation by extracellular calcium of adrenergic nerves and vascular smooth muscle. The action of the endothelium is overcome by BAY K 8644, suggesting that voltage-dependent calcium channels are important in the inhibitory role of the endothelium in both adrenergic nerves and smooth muscle cells.
Tesfamariam
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B
Robert Dawson Evans Department of Clinical Research, Boston University School of Medicine, Massachusetts 02118.
Weisbrod
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RM
Cohen
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RA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology*; D005071:Evoked Potentials / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010293:Pargyline; D003042:Cocaine; D002118:Calcium; D006854:Hydrocortisone; D009638:Norepinephrine