Upregulation of AT(1)R and iNOS in the Rostral Ventrolateral Medulla (RVLM) Is Essential for the Sympathetic Hyperactivity and Hypertension in the 2K-1C Wistar Rat Model

Autor(es)

de Oliveira-Sales, Elizabeth Barbosa ^[1] ; Nishi, Erika Emy ^[1] ; Boim, Mirian Aparecida ^[2] ; Dolnikoff, Miriam Sterman ^[1] ; Bergamaschi, Cassia T. ^[3] ; Campos, Ruy R. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Dept Physiol, Div Cardiovasc, Sao Paulo - Brazil

^[2] Univ Fed Sao Paulo, Div Nephrol, Dept Med, Sao Paulo - Brazil

^[3] Fed Univ Sao Paulo Baixada Santista, Dept Biosci, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AMERICAN JOURNAL OF HYPERTENSION; v. 23, n. 7, p. 708-715, JUL 2010.
• Citações Web of Science: 37

Resumo

BACKGROUND We hypothesized that upregulation of angiotensin type 1 receptor (AT, R) and inducible nitric oxide (NO) synthase (iNOS) within the rostral ventrolateral medulla (RVLM) could contribute to two-kidney, one-clip (2K-1C) hypertension. METHODS The experiments were performed in male Wistar rats, 6 weeks after the renal surgery. The animals were divided into control (SHAM, n = 18) and hypertensive groups (2K-1C, n = 18). Bilateral tissue punches were taken from sections containing the RVLM to perform iNOS gene expression analyses by the real-time PCR technique, and AT(1)R and iNOS protein expression analyses by western blotting. In addition, we injected losartan (1 nmol), an AT(1)R antagonist, and aminoguanidine (250 pmol), an iNOS inhibitor, bilaterally into the RVLM to analyze the mean arterial pressure (MAP) and renal sympathetic nerve activity (rSNA). RESULTS iNOS mRNA expression levels were greater (P < 0.05) in the 2K-1C group compared to the SHAM group. Furthermore, the AT(1)R and iNOS protein expression were significantly increased in the RVLM of 2K-1C rats compared to SHAM rats. Injection of losartan into the RVLM reduced the MAP (11%) and rSNA (18%) only in the 2K-1C rats, whereas injection of aminoguanidine in the same region decreased the MAP (31%) and rSNA (34%) in hypertensive rats. CONCLUSIONS The present study suggests that upregulation of AT(1)R and iNOS in the RVLM is important in the maintenance of high blood pressure and renal sympathetic activation in 2K-1C hypertension. (AU)

• Processo FAPESP: 05/60151-6 - Papel do estresse oxidativo na geracao da atividade vasomotora simpatica na hipertensao renovascular.
• Beneficiário: Elizabeth Barbosa de Oliveira-Sales
• Modalidade de apoio: Bolsas no Brasil - Doutorado