Losartan and isoproterenol promote alterations in the local renin-angiotensin system of rat salivary glands

Autor(es)

Cano, Isadora Prado ^[1] ; Dionisio, Thiago Jose ^[2] ; Cestari, Tania Mary ^[2] ; Calvo, Adriana Maria ^[2] ; Colombini-Ishikiriama, Bella Luna ^[2] ; Cardoso Faria, Flavio Augusto ^{[3, 4]} ; Siqueira, Walter Luiz ^{[3, 4]} ; Santos, Carlos Ferreira ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Bauru Sch Dent, Dept Prosthodont & Periodontol, Bauru, SP - Brazil

^[2] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru, SP - Brazil

^[3] Univ Western Ontario, Schulich Sch Med & Dent, Dept Biochem, London, ON - Canada

^[4] Univ Western Ontario, Schulich Sch Med & Dent, Sch Dent, London, ON - Canada

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 14, n. 5 MAY 22 2019.
• Citações Web of Science: 0

Resumo

Renin-angiotensin system (RAS) systemically or locally collaborates with tissue homeostasis, growth and development, which has been extensively studied for its pharmacological implications. This study was primarily aimed at finding and characterizing local RAS in rat parotid, sublingual and submandibular glands. It was also hypothesized that vasoactive drugs could affect the expression of RAS targets, as well as saliva flow and its composition. Therefore, another objective of this study was to compare the effects of losartan (angiotensin II receptor blocker) and isoproterenol (beta-adrenergic receptor agonist). Forty-one Wistar rats were divided into three groups and administered a daily intraperitoneal dose of saline, losartan or isoproterenol solutions for one week. The following RAS targets were studied using qPCR: renin (REN), angiotensinogen (AGT), angiotensin converting enzyme (ACE), ACE-2, elastase-2 (ELA-2), AT1-a and MAS receptors, using RPL-13 as a reference gene. Morphology of glands was analyzed by immunohistochemistry using REN, ACE, ACE-2, AT1, AT2 and MAS antibodies. The volume and total protein content of saliva were measured. Our results revealed that ACE, ACE-2, AT1-a, AT2 and MAS receptors were expressed in all salivary gland samples, but REN and ELA-2 were absent. Losartan decreased mRNA expression of RAS targets in parotid (MAS) and submandibular glands (ACE and both AT receptors), without affecting morphological alterations, and significantly decreased saliva and total protein secretions. Isoproterenol treatment affected gene expression profiles in parotid (ACE, ACE-2, AT1-a, MAS, AGT), and submandibular (ACE, AT2, AGT) glands, thus promoting acinar hypertrophy in serous acini, without significant changes in salivary flow or total protein content. These drugs affected mainly acini, followed by duct systems and myoepithelial cells, whereas blood vessels were not affected. In conclusion, there is a local RAS in major rat salivary glands and losartan, an angiotensin II receptor blocker, affected not only the RAS-target gene expression but also decreased salivary flow and total protein content. (AU)

• Processo FAPESP: 14/12975-9 - O sistema renina-angiotensina local em glândulas salivares de rato: alterações medicamentosas
• Beneficiário: Isadora Prado Cano
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 14/22379-4 - O sistema renina-angiotensina local em glândulas salivares de rato: alterações medicamentosas
• Beneficiário: Isadora Prado Cano
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Iniciação Científica
• Processo FAPESP: 17/17747-2 - Avaliação qualitativa e quantitativa de citocinas no sulco gengival de dentes que receberão coroas metalocerâmicas em diferentes fases dos procedimentos clínicos, em pacientes usuários de drogas antagonistas do receptor AT1A para Angiotensina II
• Beneficiário: Isadora Prado Cano
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático