Endothelium inhibits responses of rabbit carotid artery to adrenergic nerve stimulation.
Transmural electrical stimulation of isolated ring segments of the rabbit carotid artery caused frequency-dependent contractions; these were blocked by tetrodotoxin or prazosin. Mechanical or chemical removal of the endothelium markedly augmented responses to electrical stimulation. Inhibition of norepinephrine uptake and metabolism with cocaine, hydrocortisone, and pargyline increased contractions in rings with endothelium more than those without endothelium, but responses remained greater in rings denuded of endothelium. Methylene blue, an inhibitor of guanylate cyclase, enhanced responses to electrical stimulation of rings with intact endothelium only. Combined inhibition of guanylate cyclase and norepinephrine disposition increased the contractions and abolished the difference between the responses of rings with and without endothelium. In a perfusion-cascade system, the perfusate of donor segments with endothelium relaxed a bioassay ring without endothelium. Electrical stimulation of the segment caused no further relaxation of the bioassay ring. However, contractions caused by electrically stimulating the bioassay ring were depressed during superfusion with the perfusate of segments with, but not without, endothelium, indicating that vasodilators spontaneously released from the endothelium inhibit responses to nerve stimulation. These observations suggest that inhibition by the endothelium of the response to adrenergic nerve stimulation results from 1) spontaneous release of endothelium-derived vasodilators and 2) disposition of norepinephrine by the endothelial cells.
D000818:Animals; D001681:Biological Assay; D001688:Biological Products / Q000032:analysis; D002339:Carotid Arteries / Q000187:drug effects / Q000294:innervation*; D003042:Cocaine / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D004730:Endothelium, Vascular / Q000502:physiology*; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000378:metabolism; D009569:Nitric Oxide; D009638:Norepinephrine / Q000378:metabolism; D010293:Pargyline / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects
D001688:Biological Products; D009569:Nitric Oxide; D010293:Pargyline; D003042:Cocaine; D008751:Methylene Blue; D006854:Hydrocortisone; D009638:Norepinephrine; D011224:Prazosin