title: The role of endothelium-derived nitric oxide in acetylcholine-induced coronary vasoconstriction in closed-chest pigs.
abstract: BACKGROUND
  The effects of an inhibitor of endothelium-derived nitric oxide on acetylcholine (ACh)-induced coronary vasoconstriction were examined in 13 anesthetized closed-chest pigs.
  
  
  METHODS
  Coronary blood flow was measured using a previously implanted ultrasonic transmit-time flow probe. The diameter of the large epicardial coronary arteries was assessed by coronary arteriography.
  
  
  RESULTS
  Intracoronary infusions of ACh (0.1, 0.3, and 1.0 micrograms/kg/min) resulted in dose-dependent decreases in coronary blood flow. Arterial pressure and heart rate were minimally altered by ACh. The high dose of ACh decreased coronary blood flow by 67 +/- 11% and caused myocardial ischemia, demonstrated by ST-segment elevation. Coronary arteriograms revealed diffuse narrowing of peripheral coronary arteries and a filling delay of the contrast medium evoked with ACh. Vasospasm of the large epicardial coronary arteries was not observed. The decreases in coronary blood flow with ACh were inhibited by atropine (0.2 mg). Intracoronary administration of an inhibitor of endothelium-derived nitric oxide, NW-nitro-L-arginine (NNLA, 1.0 mg/kg), slightly increased arterial pressure but did not change baseline coronary blood flow. The percentage decreases in coronary blood flow induced by ACh were significantly augmented by NNLA administration, but those induced by prostaglandin F2 alpha (0.5 microgram/kg/min) were not affected by NNLA. The response of the large coronary arteries to ACh was not altered by NNLA.
  
  
  CONCLUSIONS
  Our results suggest that, in pigs, ACh decreased coronary blood flow and caused myocardial ischemia as a result of the direct cholinergic vasoconstriction of peripheral small coronary arteries. The augmentation of ACh-induced coronary vasoconstriction by NNLA suggests that ACh facilitated the release of endothelium-derived nitric oxide, which attenuated the direct coronary vasoconstriction induced by ACh.
authors.affiliation: Research Institute of Angiocardiology and Cardiovascular Clinic, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Egashira
authors.forename: T
authors.initials: T
authors.lastname: Fukai
authors.forename: Y
authors.initials: Y
authors.lastname: Ohara
authors.forename: H
authors.initials: H
authors.lastname: Kasuya
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: A
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester