Regulation of myocardial beta-adrenergic receptor function in adult and neonatal rabbits.
beta-Adrenergic receptor (betaAR) desensitization is the decrease in response following sustained agonist stimulation by catecholamines. While developmental changes in betaAR response have been well documented in the mammalian heart, much less is known regarding the regulation of betaAR function in immature hearts. The purpose of the present study was to determine whether there are developmental differences in myocardial betaAR desensitization. We used an isolated heart preparation to examine the betaAR-mediated inotropic response before and after sustained exposure to 1 microM isoproterenol in adult and neonatal rabbits. We also assayed the adenylyl cyclase activity and performed radioligand-binding studies to determine betaAR characteristics in adult and neonatal ventricular tissues with and without exposure to isoproterenol. Both adult and neonatal rabbit hearts showed a concentration-dependent increase in systolic function, namely, isovolumic left ventricular developed pressure (LVDP) and maximal positive dP/dt of LVDP (dP/dt(max)) in response to isoproterenol. Adults, however, showed a significantly greater response than neonates. After sustained exposure to isoproterenol, the subsequent betaAR-mediated responses in LVDP and dP/dt(max) were significantly attenuated in adults, but much less so in neonates. The adenylyl cyclase activity in response to isoproterenol was significantly different between adult, but comparable in neonatal tissues both exposed or not to isoproterenol. The total betaAR density was higher in neonatal than in adult tissues without isoproterenol exposure, but there was no significant change in betaAR density in either group following isoproterenol exposure. In addition, isoproterenol exposure increased the amount of the inhibitory G protein in adult, but not neonatal tissues. Our results suggest that there were developmental differences in myocardial betaAR functional responses in betaAR desensitization.
Sun
L S
LS
Department of Anesthesiology and Pediatrics, Columbia University College of Physicians and Surgeons, New York, N.Y., USA. lss4@columbia.edu
D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000032:analysis; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D011312:Pressure; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol