Effect of an inhibitor of nitric oxide synthase on neural relaxation of human bronchi.
This study examines the roles of peptides and nitric oxide (NO) as mediators of inhibitory nonadrenergic, noncholinergic (NANCi) neurons in human and guinea pig airways in vitro. Tissues were contracted with 0.3 microM methacholine (MCh) and relaxation studied before and after the addition of the peptidase alpha-chymotrypsin (alpha-CT) (2 U/ml) and NG-nitro-L-arginine methyl ester (L-NAME 0.1-1.1 mM), an inhibitor of NO synthase, the enzyme catalyzing the formation of NO. alpha-CT alone, in comparison to parallel time controls, inhibited control relaxation to electrical field stimulation (EFS) by 29.2 +/- 8.6% in guinea pig tracheae (n = 9), whereas a small augmentation of relaxation was observed in human bronchi (n = 7). L-NAME inhibited the NANCi response in both guinea pig tracheae and human bronchi: in guinea pig tracheae, maximal inhibition of the alpha-CT-insensitive relaxation was 59.3 +/- 11.5% (SE, P = 0.003) at low frequencies (4-16 Hz) and 28.6 +/- 8.9% (P = 0.08) at 32 Hz; in human bronchi, the maximal inhibition was 37.7 +/- 9.3% (P = 0.008) at 8 or 16 Hz, and 37.9 +/- 5.9% (P = 0.005) at 32 Hz. Inhibition was greater after repeated baseline EFS for 90 min before initiation of contraction with MCh and addition of L-NAME (59.8 +/- 13.9% after repeated baseline EFS, n = 4; vs. 34.9 +/- 6.2% without repeated baseline EFS, n = 9, P = 0.025). Relaxant responses to sodium nitroprusside, vasoactive intestinal peptide, and isoproterenol were not affected by L-NAME. L-Arginine (10 mM), a precursor of NO, partially reversed the effect of L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
Bai
T R
TR
University of British Columbia Pulmonary Research Laboratory, St. Paul's Hospital, Vancouver, Canada.
Bramley
A M
AM
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D002918:Chymotrypsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008175:Lung Neoplasms / Q000601:surgery; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D016210:Methacholine Chloride; D009599:Nitroprusside; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D002918:Chymotrypsin; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester