Endothelial cells inhibit the vascular response to adrenergic nerve stimulation by a receptor-mediated mechanism.
Rabbit central ear arteries, with and without endothelium, were perfused at a constant flow rate and the perfusion pressure was measured as an index of the vessel resistance. Transmural nerve stimulation (TNS) induced a frequency-dependent increase in perfusion pressure in all vessels that was blocked by tetrodotoxin, phentolamine, and prazosin. Removal of endothelium significantly enhanced contractions induced by TNS. The inhibitory effect of endothelium was not modified by indomethacin but was abolished by hemoglobin, indicating that endothelium-derived relaxant factor (EDRF) was the vasodilator involved. The endothelium-dependent inhibitory effect (rubbed vessel minus control vessel contractions) increased with time during the first 10-20 s after the beginning of TNS, and was frequency dependent and inhibited by low doses of phentolamine, which suggest a receptor-mediated mechanism. To analyze whether amine neurotransmitters are able to permeate the artery wall and contact the endothelial cell membrane, the passage of [3H]acetylcholine from the abluminal side to the lumen was studied in intact vessels. [3H]acetylcholine readily permeated the vessel wall, as assessed by radioautography, and appeared in the perfusion fluid at a concentration that explains the relaxation induced by perivascular acetylcholine. These data suggest that endothelial cells modulate the effect of perivascular neurotransmitters by a receptor-mediated mechanism. In the case of the sympathetic innervation, such modulation would be more relevant at low levels of transmitter release and would be minimized during intense sympathetic stimulation.
González
C
C
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Martin
C
C
Hamel
E
E
Galea
E
E
Gómez
B
B
Lluch
S
S
Estrada
C
C
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D006426:Hemicholinium 3 / Q000494:pharmacology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D010646:Phentolamine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
D011941:Receptors, Adrenergic; D006426:Hemicholinium 3; D009569:Nitric Oxide; D013779:Tetrodotoxin; D010830:Physostigmine; D000109:Acetylcholine; D009638:Norepinephrine; D011224:Prazosin; D010646:Phentolamine