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

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

Author Oliveira-Sales, Elizabeth Barbosa de Autor UNIFESP Google Scholar
Nishi, Erika Emy Autor UNIFESP Google Scholar
Boim, Mirian Aparecida Autor UNIFESP Google Scholar
Dolnikoff, Miriam Sterman Autor UNIFESP Google Scholar
Bergamaschi, Cassia T. Autor UNIFESP Google Scholar
Campos, Ruy R. Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Abstract BACKGROUNDWe 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.METHODSThe 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).RESULTSiNOS 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.CONCLUSIONSThe 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.
Keywords angiotensin receptors
blood pressure
genes
Goldblatt hypertension
hypertension
nitric oxide
rats
RVLM
sympathetic nervous system
Language English
Sponsor Fundacao de Amparo Pesquisa do Estado de São Paulo
Grant number Fundacao de Amparo Pesquisa do Estado de São Paulo: 05/60151-6
Date 2010-07-01
Published in American Journal of Hypertension. New York: Nature Publishing Group, v. 23, n. 7, p. 708-715, 2010.
ISSN 0895-7061 (Sherpa/Romeo, impact factor)
Publisher Nature Publishing Group
Extent 708-715
Origin http://dx.doi.org/10.1038/ajh.2010.64
Access rights Closed access
Type Article
Web of Science ID WOS:000279119700005
URI http://repositorio.unifesp.br/handle/11600/32691

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