title: Endothelium-dependent nonadrenergic, noncholinergic neural relaxation in guinea pig pulmonary artery.
abstract: The presence and the possible mechanism of action of the inhibitory nonadrenergic, noncholinergic nerve system (i-NANC) were investigated in guinea pig pulmonary artery (PA) precontracted with U44069 (a thromboxane analog). In the presence of alpha adrenergic blockage, electrical field stimulation induced a frequency-dependent, tetrodotoxin-sensitive relaxation. This relaxation was reduced by 9.1 +/- 1.9 and 19.4 +/- 2.8% by atropine (1 microM) and combined atropine and propranolol (both 1 microM), indicating that the main component is mediated by i-NANC neural mechanisms. In the branch PA rings, this i-NANC relaxation was unaffected by pretreatment with a cyclooxygenase inhibitor (indomethacin, 10 microM), 5-lipoxygenase inhibitor (A63162, 1 microM) or substance P desensitization, but was inhibited markedly by the P2y-purinoceptor antagonist reactive blue 2 (30 microM) and slightly potentiated by the peptidase alpha-chymotrypsin (2 U/ml). L-NG-monomethyl-arginine(L-NMMA), a nitric oxide synthesis inhibitor, caused a concentration-dependent inhibition of the i-NANC relaxation (53.9 +/- 4.1% at 100 microM), but had no effect on equivalent nitroprusside-induced relaxation. The inhibitory effect of L-NMMA was reversed completely by L-arginine (300 microM), but not by D-arginine (300 microM). Removal of vascular endothelium greatly reduced the i-NANC relaxation in the branch PA rings, but had no effect on i-NANC relaxation in main PA rings. Both in vivo capsaicinization and in vitro desensitization with capsaicin (1 microM) caused a significant reduction of the i-NANC relaxation in main PA, but had no significant effect in the branch PA.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Thoracic Medicine, National Heart and Lung Institute, London, England.
authors.forename: S F
authors.initials: SF
authors.lastname: Liu
authors.forename: D E
authors.initials: DE
authors.lastname: Crawley
authors.forename: T W
authors.initials: TW
authors.lastname: Evans
authors.forename: P J
authors.initials: PJ
authors.lastname: Barnes
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D002918:Chymotrypsin / Q000494:pharmacology; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010647:Phenyl Ethers; D011433:Propranolol / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D019323:omega-N-Methylarginine
chemical_list: D000081:Acetamides; D016859:Lipoxygenase Inhibitors; D010647:Phenyl Ethers; D011450:Prostaglandin Endoperoxides, Synthetic; C068663:N-hydroxy-N-(1-(4-(phenylmethoxy)phenyl)ethyl)-acetamide; D019323:omega-N-Methylarginine; D014660:Vasoactive Intestinal Peptide; C028429:U 44069; D001285:Atropine; D000255:Adenosine Triphosphate; D001120:Arginine; D011433:Propranolol; D002918:Chymotrypsin; D002211:Capsaicin; D007213:Indomethacin