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We have argued that there may be an interaction between the (-) and (+) isoproterenol at the level of beta-adrenoceptors and/or the pharmacokinetics. In order to investigate this possibility, the cardiac responses to (-) isoproterenol were studied in the absence and presence of (+) isomer in vivo and in vitro using guinea pigs, and were compared with those to (±) isoproterenol.
Aerosol inhalation of 0.25 % (-) isoproterenol induced the increase of heart rate (HR) and decrease of diastolic blood pressure (DBP), and cardiovascular responses to (-) isoproterenol were not significantly different from those to corresponding dose (0.5%) of ( ±) isoproterenol. In contrast, aerosol inhalation of 0.25% (+) isoproterenol induced a slight cardiovascular responses but there was no significant difference between the cardiovascular responses to 0.25 % (+) isoproterenol and saline inhalations. The cardiovascular responses to 0.25 % (-) isoproterenol inhalation were not affected by the concomitant presence of 0.25% (+) isomer. However, prior inhalation of 0.25% (+) isomer reduced the increase response of HR but not the decrease response of DBP to aerosol 0.25% (-) isoproterenol.,Furthermore, the increase response of HR to intravenously administered (±) isoproterenol (1 mcg/kg) was also reduced by prior inhalation of 0.25 % ( + ) isoproterenol. In isolated atria, the concentration-response curves and EC50 values for positive chronotropic and inotropic responses to (- ) and ( ± ) isoproterenol were not sig nificantly different, and as was the case in vivo, the cardiac stimulating potency of (-) isomer was not significantly affected by the presence of ( + ) isomer which was 30-fold less potent than (- ) isomer in the isolated atria from guinea pigs.
The above results suggest that the prior inhalation of ( +) isoproterenol reduces the cardiac responses to aerosol ( - ) isoproterenol which may result from desensitization rather than antagonism at the cardiac beta-adrenoceptors by ( +) isoproterenol. Further mechanism of the cardiac hyporesponsiveness to ( - ) isoproterenol by the prior treatment of ( + ) isoproterenol remains to be elucidated.
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