Evidence for reduction of bradykinin-induced bronchoconstriction in guinea-pigs by release of nitric oxide.
1. In this study the influence of nitric oxide (NO) on the bronchoconstriction induced by bradykinin in anaesthetized and artifically ventilated guinea-pigs pretreated with atropine was investigated. 2. Aerosol administration of bradykinin (0.1-1 mM, 40 breaths) caused a dose-dependent increase in lung resistance (RL): maximum increase in RL was 2.5 fold the baseline value. Pretreatment with aerosolized NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA) (1 mM, 10 breaths every 5 min for 30 min), NO synthase inhibitors, markedly increased the bronchoconstrictor response to bradykinin. L-Arginine, but not D-arginine, (3 mM, 10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to aerosolized bradykinin caused by L-NAME and L-NMMA. 3. L-NAME (1 mM, 10 breaths every 5 min for 30 min) increased the bronchoconstriction induced by intravenous bradykinin (1-10 nmol kg-1). L-Arginine, but not D-arginine, (10 breaths every 5 min for 30 min) reversed the hyperresponsiveness to intravenous bradykinin caused by L-NAME. 4. The increase in RL induced by capsaicin, either aerosol (10 microM, 10 breaths) or i.v. (20 nmol kg-1) was not affected by L-NAME (1 mM, 10 breaths every 5 min for 30 min). Acute resection of the vagi did not affect the bronchoconstriction evoked by bradykinin in guinea-pigs, either in the absence or presence of L-NAME (1 mM, 10 breaths every 5 min for 30 min). 4. These results suggest that, irrespective of the route of administration, bradykinin releases NO or a related molecule which exerts a bronchodilator action that opposes the bronchoconstrictor mechanisms activated by bradykinin itself.
Ricciardolo
F L
FL
Cardiovascular Research Institute, University of California, San Francisco 94143-0130.
Nadel
J A
JA
Yoshihara
S
S
Geppetti
P
P
Yoishihara
S
S
D000336:Aerosols; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000187:drug effects; D014628:Vagotomy; D014655:Vascular Resistance / Q000187:drug effects; D019323:omega-N-Methylarginine
D000336:Aerosols; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D002211:Capsaicin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester