Development of cardiovascular responses to sympathomimetic amines and autonomic blockade in the unanesthetized fetus

Abstract

The cardiovascular effects of phenylephrine or ephedrine alone and after autonomic blockade were studied in the chronically cannulaied fetal lamb (100–145 days), the newborn lamb, and adult sheep. As gestation advanced, phenylephrine and ephedrine produced an increasing pressor response before and after pretreatment with atropine (1 mg/kg). Compared with the fetus, the magnitudes of the pressor responses were somewhat greater in the newborn and much larger in the adult. Both drugs produced a reflex bradycardia in the unatropinized fetus which in the case of ephedrine was followed by a tachycardia. Pretreatment with atropine resulted in an immediate tachycardia after ephedrine but not after phenylephrine administration. Pretreatment with phentolamine (0.15 mg/kg) produced about a 55% inhibition of the phenylcphrine pressor response in both the fetus and adult, suggesting a linear relationship between body weight and number of α-adrenergic receptors. Pretreatment with metoprolol blocked the tachycardia associated with ephedrine administration to unatropinized fetuses. In summary, the increase in the magnitude of the pressor response to phenylephrine suggested development of the receptor–effector system. The greater development of the response to ephedrine suggested that there was an increasing amount of noradrenaline being released with advancing gestation.