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 ß-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 ß-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 ß2-adrenoceptor blockade with ICI118,551; (d) neonatal atria showed greater ß2-adrenoceptor mRNA levels, and more prominent positive chronotropic response to the ß2- and ß3-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 ß2- and ß3-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 ß1-adrenoceptor signaling in the neonate, increasing the responsiveness to endogenous and exogenous ß2-adrenoceptor agonists.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Atrial Function, Right/drug effects , Heart Atria/drug effects , Heart Rate/drug effects , Norepinephrine/pharmacology , Receptors, Adrenergic, beta/drug effects , Adrenergic beta-Agonists/metabolism , Adrenergic beta-Antagonists/pharmacology , Age Factors , Animals , Animals, Newborn , Dose-Response Relationship, Drug , Female , Gene Expression Regulation, Developmental , Heart Atria/innervation , Heart Atria/metabolism , Male , Norepinephrine/metabolism , Norepinephrine Plasma Membrane Transport Proteins/metabolism , RNA, Messenger/metabolism , Rats, Wistar , Receptors, Adrenergic, beta/genetics , Receptors, Adrenergic, beta/metabolism , Receptors, Adrenergic, beta-1/drug effects , Receptors, Adrenergic, beta-1/metabolism , Receptors, Adrenergic, beta-2/drug effects , Receptors, Adrenergic, beta-2/metabolism , Receptors, Adrenergic, beta-3/drug effects , Receptors, Adrenergic, beta-3/metabolism , Signal Transduction/drug effectsABSTRACT
Calcium ions play an important role in several cell functions, from fertilization to cell death. The cytosolic Ca(2+) concentration is much lower than the extracellular concentration ([Ca(2+)](o)). The latter may markedly affect Ca(2+) fluxes across the cell membrane and thus the cellular Ca(2+) load. Thus, when working with preparations in vitro, it is important to keep [Ca(2+)](o) close to the in vivo value. In this study, we determined the calcemia in immature rats, for which values are currently unavailable, and investigated how supraphysiological [Ca(2+)](o) affects myocardial Ca(2+) handling. Blood ionized [Ca(2+)] was similar in neonatal (2-5 days old) and adults Wistar rats (1.28 ± 0.03 and 1.31 ± 0.03 mmol/l; n=6 and 5, respectively, P>0.37), and lower than the [Ca(2+)](o) range often used in experiments with neonatal myocardial preparations. Cytosolic Ca(2+) transients, measured with indo-1 in neonatal ventricular myocytes, were enhanced by an increase in [Ca(2+)](o) from 1.2 to 2 mM, which also increased the Ca(2+) content in the sarcoplasmic reticulum (SR), and changed the pattern of competition between the main transporters that remove Ca(2+) from the cytosol (SR Ca(2+)-ATPase and Na(+)/Ca(2+) exchanger). These observations stress the importance of using physiological [Ca(2+)](o) values for reliability of results. It is expected that the present calcemia data, reported for the first time in immature rats, may contribute to the refinement of in vitro experiments with neonatal rat preparations.
Subject(s)
Calcium/blood , Myocytes, Cardiac/metabolism , Sarcoplasmic Reticulum/metabolism , Sodium-Calcium Exchanger/metabolism , Action Potentials , Animals , Animals, Newborn , Caffeine/pharmacology , Calcium/metabolism , Cytosol/metabolism , Female , Indoles/chemistry , Male , Myocardial Contraction , Rats , Rats, Wistar , Specific Pathogen-Free OrganismsABSTRACT
Syphacia sp. is a common intestinal parasite in conventionally-housed laboratory rodents. Although gross lesions are rare in oxyuriasis, it is possible that more subtle changes may develop, which may affect research results. In this study, we analysed the responsiveness to beta-adrenergic stimulation by isoproterenol (ISO) of left atria isolated from Syphacia-infested (SYPH) and control, non-infested adult male Wistar rats (CONT). In the non-infested animals, ISO pD(2) was not significantly changed by ivermectin treatment. Whereas the maximal inotropic response to ISO was not significantly affected, the pD(2) value was decreased in SYPH (7.61 +/- 0.09, n = 7, vs 8.21 +/- 0.25 in CONT, n = 5, P < 0.05), indicating lower sensitivity to beta-adrenergic stimulation. This change was similar to that caused by a classic stressor, namely repeated immobilization, in non-infested rats (IMMO). In this group, ISO pD(2) was 7.62 +/- 0.14, n = 6 (P < 0.05 with relation to CONT). The results indicate that infestation with Syphacia sp. is as effective as immobilization at diminishing cardiac reactivity to beta-adrenergic stimulation. It is thus possible that oxyuriasis may affect the response of other tissues to physiological modulators.
