The role of sensory nerves in propranolol-induced bronchial hyperresponsiveness in the guinea-pig.
The racemic mixture propranolol (RS-(+/-)-, and the S-(-)- and R-(+)-) isomers of propranolol have been shown to induce bronchial hyperresponsiveness in the guinea-pig unrelated to beta-adrenoreceptor occupancy, that is attenuated by vagal section and mediated via the generation of 5-lipoxygenase metabolites of arachidonic acid. We have investigated the role of sensory nerves in propranolol-induced bronchial hyperresponsiveness in guinea-pigs. Airways responsiveness to acetylcholine, bradykinin and bombesin was determined before and 10 min after intravenous infusion with RS-(+/-)-, S-(-)- and R-(+)-propranolol (1 mg/kg) in vehicle and capsaicin-treated guinea-pigs. Propranolol (1 mg/kg, iv) significantly augmented the bronchoconstrictor response to acetylcholine, bradykinin and bombesin (P<0.001), an effect that was observed for RS-(+/-)-, S-(-)- and R-(+)-propranolol. In capsaicin-treated animals, the increased airways responsiveness to acetylcholine following intravenous infusion of S-(-)-propranolol was significantly inhibited. Capsaicin treatment tended to reduce the increase in airways responsiveness to bradykinin following infusion with R-(+)-propranolol, but was only significant for the highest dose used. Similarly, capsaicin treatment had no effect on the ability of RS-(+/-)-, S-(-)- and R-(+)-propranolol to enhance the bronchoconstrictor response to bombesin. Our results suggest that propranolol-induced bronchial hyperresponsiveness to certain spasmogens is in part mediated by the action of capsaicin-sensitive nerves.
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The Sackler Institute of Pulmonary Pharmacology Division of Pharmacology and Therapeutics, King's College London, Manresa Road, London, SW3 6LX, UK.
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D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000503:physiopathology*; D002211:Capsaicin / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology*; D013565:Sympatholytics / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D013565:Sympatholytics; D014665:Vasodilator Agents; D011433:Propranolol; D000109:Acetylcholine; D001839:Bombesin; D002211:Capsaicin; D001920:Bradykinin