Development of cardiovascular responses to noradrenaline, adrenaline, normetanepnrine, and metanephrine in the unanesthetized fetus

Abstract

The cardiovascular responses to the catecholamines noradrenaline (NA) and adrenaline (A) and their metabolites normetanephrine (NM) and metanephrine (M) were determined in the chronically prepared ovine fetus (112–145 days), newborn lamb (6–12 or 96 h), and adult sheep to assess the development of responsiveness to these biogenic amines. With NA, NM, and M there was a gradual significant increase in the pressor response with advancing gestation and a larger increase between late term and the newborn period where the response was still only about one-half of the adult. With A, there was only a significant increase in pressor response after birth to a level about one-half the adult response. In all age groups the pressor response to these amines was accompanied by bradycardia which was especially marked with A; pretreatment with atropine blocked the reflex bradycardia and resulted in an increase in the magnitude of the pressor response. The duration of the NA pressor response decreased only slightly in the near-term fetus but decreased markedly in the newborn lamb to a value similar to the adult. There were no differences in any age groups in the ratios of the responses to NA and A and their respective metabolites. These data indicate gradual development of the responsiveness of the ovine cardiovascular system to endogenous pressor amines over the last third of gestation with a further increase immediately after birth to a level still below the adult, early development of alpha receptors capable of discriminating neurohormones from metabolites and rapid development at or near term of mechanisms involved in terminating the action of NA.