title: Atrial chronotropic reactivity to catecholamines in neonatal rats: Contribution of β-adrenoceptor subtypes.
abstract: 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 β-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 quantitation of the transcripts of proteins involved in β-adrenergic signaling. The main results were: (a) the maximum response (Rmax) to norepinephrine increased with age, whereas sensitivity decreased; (b) age-dependent differences in sensitivity to norepinephrine were abolished by inhibition of the neuronal norepinephrine transporter; (c) Rmax to isoproterenol was similar in immature and adult atria, and depressed only in the former by β2-adrenoceptor blockade with ICI118,551; (d) neonatal atria showed greater β2-adrenoceptor mRNA levels, and more prominent positive chronotropic response to the β2- and β3-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 β2- and β3-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 β1-adrenoceptor signaling in the neonate, increasing the responsiveness to endogenous and exogenous β2-adrenoceptor agonists.
authors.affiliation: Center for Biomedical Engineering, University of Campinas (UNICAMP), R. Alexander Fleming 163, 13083-881 Campinas, Brazil; Department of Pharmacology, School of Medical Sciences, UNICAMP, Brazil.
authors.forename: Elizângela S
authors.initials: ES
authors.lastname: Oliveira
authors.affiliation: Brazilian Biosciences National Laboratory (LNBio), Campinas, SP, Brazil.
authors.forename: Ana H
authors.initials: AH
authors.lastname: Pereira
authors.affiliation: Brazilian Biosciences National Laboratory (LNBio), Campinas, SP, Brazil.
authors.forename: Alisson C
authors.initials: AC
authors.lastname: Cardoso
authors.affiliation: Brazilian Biosciences National Laboratory (LNBio), Campinas, SP, Brazil; Department of Medical Clinics, School of Medical Sciences, UNICAMP, Brazil.
authors.forename: Kleber G
authors.initials: KG
authors.lastname: Franchini
authors.affiliation: Center for Biomedical Engineering, University of Campinas (UNICAMP), R. Alexander Fleming 163, 13083-881 Campinas, Brazil; Department of Biomedical Engineering, School of Electrical and Computer Engineering, UNICAMP, Brazil.
authors.forename: José W M
authors.initials: JWM
authors.lastname: Bassani
authors.affiliation: Center for Biomedical Engineering, University of Campinas (UNICAMP), R. Alexander Fleming 163, 13083-881 Campinas, Brazil; Department of Pharmacology, School of Medical Sciences, UNICAMP, Brazil. Electronic address: rosana@ceb.unicamp.br.
authors.forename: Rosana A
authors.initials: RA
authors.lastname: Bassani
mesh_terms: D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D016280:Atrial Function, Right / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006325:Heart Atria / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C547789:Adrb1 protein, rat; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D050484:Norepinephrine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine
keywords: Catecholamines; Chronotropic activity; Post-natal development; Right atrium; β-Adrenoceptor subtypes