Abstract
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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
