Acetylcholine-induced release of endothelium-derived relaxing factor from lymphatic endothelial cells.
Ring segments of dog thoracic ducts precontracted with a high concentration of norepinephrine (NE) relaxed in a concentration-dependent manner in response to acetylcholine (ACh) or sodium nitroprusside (SNP). Pretreatment with atropine inhibited the ACh-induced relaxation in a competitive manner. The Schild plot showed a slope of 1.1 +/- 0.2 and a pA2 value of 10.4 +/- 0.4 (n = 6 ring segments). Removal of endothelium caused a complete inhibition of the ACh-induced relaxations in precontracted dog thoracic ducts. ACh, which failed to relax precontraction of the ring segment when mounted separately, induced relaxation in the same preparation when it was mounted as a "sandwich" with the longitudinal strip. The ACh-induced relaxations in the lymphatic preparations with endothelium were suppressed or abolished by pretreatment with oxyhemoglobin (10(-6) and 10(-5) M), methylene blue (10(-6) and 10(-5) M), and NG-monomethyl-L-arginine (3 x 10(-5) M), but the relaxations were unaffected by aspirin (10(-5) M). Pretreatment with methylene blue (10(-5) M) also caused a significant reduction of the SNP-induced relaxations in the precontracted thoracic ducts. It may be concluded that ACh-induced relaxation in dog thoracic ducts precontracted with NE is mediated by high-affinity muscarinic receptors in the lymphatic endothelial cells. Also, stimulation of the endothelial muscarinic receptors liberates a transferable endothelium-derived relaxing factor, which results in the relaxation of the lymphatic smooth muscles via the accumulation of cellular guanosine 3',5'-cyclic monophosphate.
Ohhashi
T
T
First Department of Physiology, Shinshu University School of Medicine, Matsumoto, Japan.
Takahashi
N
N
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010108:Oxyhemoglobins / Q000494:pharmacology; D013897:Thoracic Duct / Q000187:drug effects / Q000502:physiology*; D019323:omega-N-Methylarginine
D010108:Oxyhemoglobins; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001285:Atropine; D001120:Arginine; D000109:Acetylcholine; D001241:Aspirin; D008751:Methylene Blue