Training-Induced Deactivation of the AT(1) Receptor Pathway Drives Autonomic Control and Heart Remodeling During the Transition From the Pre- to Hypertensive Phase in Spontaneously Hypertensive Rats

Autor(es)

Rodrigues da Costa, Tassia Santos ^[1] ; Masson, Gustavo Santos ^[1] ; dos Santos Eichler, Rosangela Aparecida ^[2] ; de Souza Silva, Juliane Cristina ^[3] ; Lacchini, Silvia ^[3] ; Michelini, Lisete Compagno ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Biomed Sci Inst, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Biomed Sci Inst, Dept Pharmacol, Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Biomed Sci Inst, Dept Anat, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CIRCULATION JOURNAL; v. 84, n. 8, p. 1294+, AUG 2020.
• Citações Web of Science: 0

Resumo

Background: The effects of hypertension and exercise training (T) on the sequential interplay between renin-angiotensin system (RAS), autonomic control and heart remodeling during the development of hypertension in spontaneously hypertensive rats (SHR), was evaluated. Methods and Results: Time course changes of these parameters were recorded in 4-week-old SHR submitted to a T or sedentary (S) protocol. Wistar Kyoto rats served as controls. Hemodynamic recordings were obtained in conscious rats at experimental weeks 0, 1, 2, 4, and 8. The left ventricle (LV) was collected to evaluate RAS gene and protein expression, cardiomyocytes' hypertrophy and collagen accumulation. Pre-hypertensive SHR exhibited augmented AT1R gene expression; at 5 weeks, they presented with elevated pressure, increased LV angiotensinogen and ACE mRNA expression, followed by sympathoexcitation (from the 8th week onwards). Marked AT1R protein content, myocytes's hypertrophy, collagen deposition and increased pressure variability were observed in 12-week-old sedentary SHR. In addition to attenuating all these effects, T activated Mas receptor expression augmented parasympathetic modulation of the heart, and delayed the onset and reduced the magnitude, but did not block the development of genetic hypertension. Conclusions: The close temporal relationship between changes in the LV ACE-Ang II-AT1R axis, autonomic control and cardiac remodeling at both the establishment of hypertension and during exercise training reveals the essential role played by the AT1R pathway in driving cardiac remodeling and autonomic modulation during the transition from the pre- to hypertensive phase. (AU)

• Processo FAPESP: 15/24935-4 - Barreira hematoencefálica e regulação autonômica na hipertensão arterial: efeitos da angiotensina ii e do treinamento aeróbio
• Beneficiário: Lisete Compagno Michelini
• Modalidade de apoio: Auxílio à Pesquisa - Regular