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

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.Fundacao de Amparo Pesquisa do Estado de São PauloUniversidade Federal de São Paulo, Dept Physiol, Div Cardiovasc, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilFed Univ São Paulo Baixada Santista, Dept Biosci, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Physiol, Div Cardiovasc, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, Dept Med, São Paulo, BrazilFed Univ São Paulo Baixada Santista, Dept Biosci, São Paulo, BrazilFundacao de Amparo Pesquisa do Estado de São Paulo: 05/60151-6Web of Scienc