科研之友
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摘要
Although increase in heart rate is a crucial determinant for enhancement of cardiac output in the neonate, information on the chronotropic reactivity to catecholamines during postnatal development is scarce. The present study was aimed at investigating the role of P-adrenoceptor subtypes and catecholamine removal mechanisms in the adrenergic chronotropic response during the early post natal period. Right atria isolated from immature (0-21 day old) and adult (4-6 month old) rats were used for determination of the responsiveness to agonists and quaraitation of the transcripts of proteins involved in beta-adrenergic signaling. The main results were: (a) the maximum response (R-max) to norepinephrine increased with age, whereas sensitivity decreased; (b) age dependent differences in sensitivity to nor epinephrine were abolished by inhibition of the neuronal norepinephrine transporter; (c) R-max to isoproterenol was similar in immature and adult atria, and depressed only in the former by beta(2)-adrenoceptor blockade with ICI118,551; (d) neonatal atria showed greater beta(2)-adrenoceptor mRNA levels, and more prominent positive chronotropic response to the beta(2)- and beta(3)-adrenoceptor agonists zinterol and YM178, respectively (nanomolar range); (e) in atria of immature rats, transcript levels of the extraneuronal monoamine transporter were lower, and its inhibition did not affect sensitivity to isoproterenol; and (f) reactivity to forskolin and 3-isobutyl-1-methylxanthine was not affected by age. The increased beta(2)- and beta(3)-adrenoceptor participation in the adrenergic chronotropic response, in addition to weaker catecholamine removal, may compensate for the immature cardiac innervation and the apparently reduced efficiency of beta(1)-adrenoceptor signaling in the neonate, increasing the responsiveness to endogenous and exogenous beta(2)-adrenoceptor agonists.
- 出版日期2015-10-5
