Catecholamine and beta-adrenoceptor influences on airway reactivity to antigen in guinea pigs.
The aim of the present study was to analyze the increased airway reactivity to antigen induced by beta-adrenoceptor blockade, adrenalectomy or medullectomy and to assess the contribution of circulating catecholamines to the increased reactivity. In anesthetized guinea pigs sensitized to ovalbumin (OA), administration of OA produced a dose-related bronchoconstriction characterized by threshold increases in airway insufflation pressure at 0.1 mg/kg i.v. and a near-maximal increase by 0.3 mg/kg i.v. Pretreatment with R(+) propranolol (0.5 mg/kg i.v.) 5 min prior to antigen did not significantly alter airway responses to antigen when compared to vehicle-treated animals. However, pretreatment with 0.5 mg/kg i.v. S(-) propranolol, racemic propranolol or nadolol markedly enhanced (10- to 15-fold) the airway response to the low-dose antigen. In addition, in guinea pigs which had been adrenalectomized, the reactivity to low-dose antigen was enhanced to a similar extent as that of beta-antagonist-treated animals when compared to sham-operated animals. Baseline plasma concentrations of epinephrine were significantly higher in sham-operate guinea pigs (1,494 +/- 223 ng/ml) when compared to adrenalectomized animals (412 +/- 44 ng/ml). Upon antigen exposure, epinephrine levels rose 5-fold (6,859 +/- 1,308 ng/ml) from baseline in sham-operated guinea pigs and were not significantly changed in adrenalectomized animals (848 +/- 208 ng/ml). Specific airway conductance measurements in conscious guinea pigs revealed that animals which had been medullectomized 2 weeks previously responded to lower provocative concentrations of aerosol OA (0.05-0.5%) than corresponding sham-operated animals. Airway reactivity to inhaled acetylcholine (0.1-1%) was similar in medullectomized and sham guinea pigs. Plasma concentrations of epinephrine were significantly lower in medullectomized guinea pigs (327 +/- 88 ng/ml) when compared to sham-operated animals (832 +/- 162 ng/ml). The results of the present study indicate that beta-adrenoceptor antagonism or changes in circulating epinephrine levels markedly alter the response to antigen in sensitized guinea pigs.
Underwood
D C
DC
Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
Matthews
J K
JK
Osborn
R R
RR
Novak
L B
LB
Bochnowicz
S
S
Meunier
L D
LD
D000315:Adrenalectomy; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D002395:Catecholamines / Q000097:blood / Q000494:pharmacology*; D004306:Dose-Response Relationship, Immunologic; D006168:Guinea Pigs; D007275:Injections, Intravenous; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D010991:Plethysmography; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D010047:Ovalbumin