Biphasic release of endothelium-derived relaxing factor(s) by acetylcholine from perfused canine femoral arteries. Characterization of muscarinic receptors.
Experiments were designed to compare the release of endothelium-derived relaxing factor(s) in response to various muscarinic receptor agonists from canine femoral arteries mounted in organ chambers or perfused in a bioassay system. In rings of femoral arteries, suspended for isometric tension recording in organ chambers, acetylcholine induced endothelium-dependent relaxations during contractions evoked by prostaglandin F2 alpha. Atropine and pirenzepine antagonized these relaxations in a competitive manner, atropine with a higher affinity (KB = 1.9 X 10(-9) M) than pirenzepine (KB = 5.4 X 10(-7) M). Carbachol and McN-A-343 also evoked endothelium-dependent relaxations, and pirenzepine inhibited these responses with a similar low potency. The order of relative potency of the agonists in organ chamber studies was acetylcholine = carbachol much greater than McN-A-343. Isolated segments of femoral arteries with endothelium were perfused (2 ml/min) with modified Krebs-Ringer-bicarbonate solution containing indomethacin; the perfusate was bioassayed for endothelium-derived relaxing factor(s) by means of a ring of coronary artery without endothelium. When infused above but not below the femoral artery, low concentrations (10(-8)-10(-7) M) of acetylcholine caused transient relaxations of the bioassay ring contracted with prostaglandin F2 alpha; higher concentrations of acetylcholine caused sustained decreases in tension. Atropine inhibited the two phases of the concentration-relaxation curve with similar potencies. Pirenzepine inhibited both phases in a competitive manner but exhibited significantly higher potency against the first- (ED50, 1.9 X 10(-9) M) than against the second-phase responses (ED50, 2.1 X 10(-7) M). Compound McN-A-343 induced only transient decreases in tension, whereas carbachol caused sustained relaxations.(ABSTRACT TRUNCATED AT 250 WORDS)
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004285:Dogs; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000378:metabolism*
D011976:Receptors, Muscarinic; D014665:Vasodilator Agents; D009569:Nitric Oxide; D010890:Pirenzepine; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D001285:Atropine; D002217:Carbachol; D000109:Acetylcholine