Nitric oxide synthase inhibitors do not potentiate contractions of guinea-pig isolated, perfused trachea to methacholine and histamine: examination of different perfusion (shear) rates.

Details

• Personal Author:
  Fedan, Jeffery S. ; Yuan LX
• Description:
  The involvement of nitric oxide (NO) in the reactivity of guinea-pig isolated airways was assessed by examining the effects of the NO synthase inhibitors (NOSI's) Nw-nitro-L-arginine methyl ester (L-NAME; 10-4 M), NG-methyl-L-arginine (L-NMMA; 10-4 M) and aminoguanidine (10-4 M) on contractions to methacholine and histamine. The isolated, perfused (34 ml/min) trachea was employed to allow separate addition of the NOSI's and agonists to the mucosai surface (via the intraluminal or "IL" perfusing Krebs) or to the serosal surface (via the extraluminal or "EL" bath). When L-NAME or L-NMMA were present in the EL bath and the methacholine or histamine were applied in the EL bath, no potentiation of the contractile responses to the agonists was observed . Likewise, contractions to methacholine and histamine added to the IL bath were not potentiated by L-NAME and L-NMMA in the IL bath. The only effects observed were an inhibition of reactivity to the agonists. Aminoguanidine, which also had no effect on basal tone, did not alter reactivity to methacholine added to the respective EL or IL bath, suggesting that the lack of potentiation by NOSI's was not peculiar to L-arginine analogs. In contrast to our findings, Nijkamp et al. have observed (ARRD 148:727, 1993) that L-arginine NOSI's increased substantially reactivity of guinea-pig perfused trachea to IL histamine. Whereas Nijkamp et al. perfused their tracheas with Krebs solution at 2 ml/min, our standard Krebs perfusion rate was 34 ml/min. To test the possibility that the opposite results of the two studies was due to the effect of shear rate on epithelial NO production, as occurs in vascular · endothelium, or due to washout of NO from the tracheal lumen by the Perfusing Krebs, we examined the effects of L-NAME on reactivity to IL histamine while perfusing at 5, 10, 20 or 25 ml/min. As was observed at the 34 ml/min flow rate, IL L-NAME did not potentiate contractions to IL histamine. Our findings suggest that the difference in the effects of L-NAME in the two guinea-pig perfused trachea experiments is not related to the influence of shear forces on epithelial NO production, or on washout of NO from the lumen. Our findings suggest that NO has little role in the regulation of airway reactivity in guinea pigs. [Description provided by NIOSH]
• Subjects:
  Animals Hypersensitivity Laboratories Methacholine Compounds Nitric Oxide Occupational Health Safety
• Keywords:
  Nitric oxide; Animals; Laboratory animals; Methacholines; Histamines
• ISSN:
  1073-449X
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  149
• NIOSHTIC Number:
  nn:20050727
• Citation:
  Am J Respir Crit Care Med 1994 Apr; 149(Abstract Issue):A593
• CAS Registry Number:
  Nitric oxide (CAS RN 10102-43-9)
• Federal Fiscal Year:
  1994
• Peer Reviewed:
  False
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/245955/cdc_245955_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]