Inotropic responses change during postnatal maturation in rabbit.
Inotropic response to four different types of pharmacological stimuli were compared in isolated right ventricular papillary muscles from newborn (24-48 h of age), immature (14-16 days), and adult (6-7 mo) rabbits. Forskolin, a direct activator of adenylate cyclase, produced a 12.5-fold increase in the maximal rate of tension development in the newborn group. The maximum response to isoproterenol was only 45% of the maximum forskolin response, suggesting incomplete physiological coupling of myocardial beta-adrenergic receptors to adenylate cyclase at birth. In contrast to the substantial inotropic response to agents that stimulate adenosine 3',5'-cyclic monophosphate (cAMP) generation (forskolin and isoproterenol), a selective inhibitor of cAMP hydrolysis (milrinone) was relatively ineffective in the newborn group. Sulmazole, a drug that enhances calcium sensitivity of the contractile proteins, produced its greatest inotropic effect in immature myocardium. Cytosolic high-affinity cAMP phosphodiesterase activity was partially purified from ventricular homogenates by anion-exchange chromatography. The kinetics of cAMP hydrolysis (Km and Vmax) and inhibitory potency of milrinone were comparable in each age group. Thus the age-related differences in inotropic responsiveness may not be attributable to postnatal changes in myocardial cytosolic high-affinity cAMP phosphodiesterase activity.
Artman
M
M
Department of Pediatrics, University of South Alabama College of Medicine, Mobile 36688.
Kithas
P A
PA
Wike
J S
JS
Strada
S J
SJ
D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D002316:Cardiotonic Agents / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000254:growth & development*; D007093:Imidazoles / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D020105:Milrinone; D009200:Myocardial Contraction / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology; D011817:Rabbits; D012016:Reference Values; D012984:Software
D002316:Cardiotonic Agents; D007093:Imidazoles; D011728:Pyridones; D005576:Colforsin; C029758:sulmazole; D020105:Milrinone; D007545:Isoproterenol