Endothelium-dependent effects of acetylcholine in rat aorta: a comparison with sodium nitroprusside and cromakalim.
1. The mechanisms involved in the mechano-inhibitory effects of acetylcholine (ACh) have been compared with those of sodium nitroprusside (SNP) and cromakalim on the rat isolated thoracic aorta. 2. Relaxations produced by ACh were endothelium-dependent, whereas those produced by SNP or cromakalim were endothelium-independent. 3. ACh, cromakalim and SNP relaxed established contractions produced by noradrenaline (NA) and KCl (20 mM) and these relaxations were well-maintained. 4. SNP was a relatively effective inhibitor of contractions produced by KCl (80 mM). ACh was relatively ineffective and cromakalim was without effect against such contractions. 5. Membrane potential and cyclic GMP concentrations were higher in tissues with an intact endothelium whereas rubbed tissues had a higher 86Rb efflux rate coefficient. 6. ACh and cromakalim produced a transient and long-lasting hyperpolarization, respectively. These changes were accompanied by increases in the 86Rb efflux rate coefficient with a time course comparable to that of the electrical changes. 7. Tissue cyclic GMP concentrations were significantly increased in the presence of ACh or SNP, whereas cromakalim had no effect. 8. Transmission electron microscopy showed the presence of endothelial cells on intact tissues. On rubbed preparations, such cells were absent and some damage to the underlying smooth muscle cells was detected. 9. It is concluded that at least two inhibitory substances are released from the endothelial cells by ACh. One of these increases tissue cyclic GMP concentrations and produces an electrically-silent relaxation. The other produces a transient hyperpolarization associated with the opening of 86Rb-permeable K-channels. This event may serve to initiate relaxation processes and to close any open voltage-dependent Ca-channels.
Taylor
S G
SG
Physiological Sciences Department, Manchester University Medical School.
Southerton
J S
JS
Weston
A H
AH
Baker
J R
JR
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000648:ultrastructure; D001578:Benzopyrans / Q000494:pharmacology*; D019806:Cromakalim; D006152:Cyclic GMP / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005292:Ferricyanides / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D008854:Microscopy, Electron; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D011189:Potassium Chloride / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes
D001578:Benzopyrans; D005292:Ferricyanides; D011758:Pyrroles; D012414:Rubidium Radioisotopes; D019806:Cromakalim; D009599:Nitroprusside; D011189:Potassium Chloride; D006152:Cyclic GMP; D000109:Acetylcholine; D009638:Norepinephrine