Inotropic effect of phenylephrine and myocardial alpha-adrenergic receptor in newborn and adult animals.
Developmental changes in the myocardial alpha-receptor density were studied using rabbit, rat and dog hearts. In all species studied, alpha-receptor density in the newborn was greater than in the adult. The inotropic effect of phenylephrine was measured using the isolated arterially perfused heart preparation of rabbit and rat. The heart was stimulated electrically at 40/min. In the presence of propranolol, phenylephrine caused a significant positive inotropic effect which was significantly less in the newborn than in the adult. Since alpha-adrenergic stimulation activates protein kinase C, the inotropic effect of protein kinase C activation was studied in the rabbit and rat using phorbol myristate acetate (PMA). PMA caused a negative inotropic effect and the decrease in contractile function in the newborn was greater than in the adult. These data suggest that myocardial alpha-receptor density decreases and the positive inotropic effect of alpha-agonist increases with development. The reasons for this discrepancy remain unclear but there may be developmental differences in the signal transduction processes of alpha-stimulation. The greater negative inotropy of protein kinase C activation in the premature heart may be one of the mechanisms of the reduced inotropy of alpha-agonist in this age group.
Nakanishi
T
T
Pediatric Cardiology, Heart Institute of Japan, Tokyo Women's Medical College.
Kamata
K
K
Nojima
K
K
Seguchi
M
M
Takao
A
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D004285:Dogs; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000254:growth & development; D009200:Myocardial Contraction / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000032:analysis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013045:Species Specificity; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; D011433:Propranolol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate