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 t...

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Published inThe American journal of physiology Vol. 255; no. 2 Pt 2; p. H335
Main Authors Artman, M, Kithas, P A, Wike, J S, Strada, S J
Format Journal Article
LanguageEnglish
Published United States 01.08.1988
Subjects
Aging
Animals
Animals, Newborn
Cardiotonic Agents - pharmacology
Colforsin - pharmacology
Female
Heart - growth & development
Imidazoles - pharmacology
Isoproterenol - pharmacology
Male
Milrinone
Myocardial Contraction - drug effects
Pyridones - pharmacology
Rabbits
Reference Values
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Summary: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.
ISSN:0002-9513
DOI:10.1152/ajpheart.1988.255.2.H335