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 react ivity to antigen induced by beta-adrenoceptor blockade, adrenalectomy or medullectomy and to assess the contribution of circulating catechol amines to the increased reactivity. In anesthetized guinea pigs sensit ized to ovalbumin (OA), administration of OA produced a dose-related b ronchoconstriction characterized by threshold increases in ah-way insu fflation 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 antig en when compared to vehicle-treated animals. However, pretreatment wit h 0.5 mg/kg i.v. S(-) propranolol, racemic propranolol or nadolol mark edly enhanced (10-to 15-fold) the airway response to the low-dose anti gen. In addition, in guinea pigs which had been adrenalectomized, the reactivity to low-dose antigen was enhanced to a similar extent as tha t of B-antagonist-treated animals when compared to sham-operated anima ls, Baseline plasma concentrations of epinephrine were significantly h igher 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 adr enalectomized 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 provocativ e concentrations of aerosol OA (0.05-0.5%) than corresponding sham-ope rated animals, Airway reactivity to inhaled acetylcholine (0.1-1%) was similar in medullectomized and sham guinea pigs. Plasma concentration s of epinephrine were significantly lower in medullectomized guinea pi gs (327 +/- 88 ng/ml) when compared to sham-operated animals (832 +/- 162 ng/ml). The results of the present study indicate that beta-adreno ceptor antagonism or changes in circulating epinephrine levels markedl y alter the response to antigen in sensitized guinea pigs.