Gender-specific impairment of in vitro sinoatrial node chronotropic responses and of myocardial ischemia tolerance in rats exposed prenatally to betamethasone

Autor(es):Mostrar menos -

Kiguti, L. R. A. ^[1] ; Borges, C. S. ^[2] ; Mueller, A. ^{[3, 1]} ; Silva, K. P. ^[1] ; Polo, C. M. ^[4] ; Rosa, J. L. ^[2] ; Silva, P. V. ^[2] ; Missassi, G. ^[2] ; Valencise, L. ^[2] ; Kempinas, W. G. ^[2] ; Pupo, A. S. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Dept Pharmacol, Inst Biosci, Campus Botucatu, Dist Rubiao Jr S-N, BR-18618689 Botucatu, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Biosci, Dept Morphol, Campus Botucatu, Dist Rubiao Jr S-N, BR-18618689 Botucatu, SP - Brazil

^[3] Univ Fed Mato Grosso, Inst Ciencias Saude, Sinop, MT - Brazil

^[4] Sao Paulo State Univ UNESP, Inst Biosci, Dept Physiol, Campus Botucatu, Dist Rubiao Jr S-N, BR-18618689 Botucatu, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Toxicology and Applied Pharmacology; v. 334, p. 66-74, NOV 1 2017.
• Citações Web of Science: 2

Resumo

Excessive fetal glucocorticoid exposure has been linked to increased susceptibility to hypertension and cardiac diseases in the adult life, a process called fetal programming. The cardiac contribution to the hypertensive phenotype of glucocorticoid-programmed progeny is less known, therefore, we investigated in vitro cardiac functional parameters from rats exposed in utero to betamethasone. Pregnant Wistar rats received vehicle (VEH) or betamethasone (BET, 0.1 mg/kg, i.m.) at gestational days 12, 13, 18 and 19. Male and female offspring were killed at post-natal day 30 and the right atrium (RA) was isolated to in vitro evaluation of drug-induced chronotropic responses. Additionally, whole hearts were retrograde-per fused in a Langendorff apparatus and infarct size in response to in vitro ischemia/reperfusion (I/R) protocol was evaluated. Male and female progeny from BET-exposed pregnant rats had reduced birth weight, a hallmark of fetal programming. Male BET-progeny had increased basal RA rate, impaired chronotropic responses to noradrenaline and adenosine, and increased myocardial damage to I/R. Though a 12-fold reduction in the negative chronotropic responses to adenosine, the effects of non-metabolisable adenosine receptor agonists 5'-(N-ethylcarboxamido)adenosine or 2-Chloro-adenosine were not different between VEH- and BET-exposed male rats. BET exposed female offspring presented no cardiac dysfunction. Prenatal BET exposure engenders male-specific impairment of sinoatrial node function and on myocardial ischemia tolerance resulting, at least in part, from an increased adenosine metabolism in the heart. In light of the importance of adenosine in the cardiac physiology our results suggest a link between reduced adenosinergic signaling and the cardiac dysfunctions observed in glucocorticoid-induced fetal programming. (AU)

• Processo FAPESP: 12/25350-1 - Efeitos da exposição in útero à betametasona sobre aspectos reprodutivos de ratos machos, com ênfase na qualidade espermática e fertilidade: uma abordagem multigeracional
• Beneficiário: Cibele dos Santos Borges
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 08/50423-7 - Adrenoceptores alfa-1A, seus ligantes e eficácias colaterais
• Beneficiário: André Sampaio Pupo
• Modalidade de apoio: Auxílio à Pesquisa - Regular