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BackgroundWe hypothesized that upregulation of angiotensin type 1 receptor (AT1R) 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 AT1R and iNOS protein expression analyses by western blotting. In addition, we injected losartan (1 nmol), an AT1R 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 AT1R 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 AT1R and iNOS in the RVLM is important in the maintenance of high blood pressure and renal sympathetic activation in 2K-1C hypertension.American Journal of Hypertension 2010; doi:10.1038/ajh.2010.64 [ABSTRACT FROM AUTHOR]

BackgroundSympathetic vasomotor hyperactivity and baroreflex dysfunction are involved in the development and maintenance of renovascular arterial hypertension. We hypothesized that angiotensin (Ang) II–dependent oxidative stress contributes to the pathophysiology of the two-kidney, one-clip (2K-1C) model.MethodsThe mean arterial pressure (MAP), baroreflex, and renal sympathetic nerve activity (rSNA) were evaluated after chronic administration of an antioxidant, vitamin C (vitC 150 mg/kg/day) in male Wistar 2K-1C rats. Additionally, the mRNA levels of Ang II subtype 1 receptor (AT1R), NAD(P)H oxidase subunits (p47phox and gp91phox), and major antioxidant enzymes were evaluated in the renal cortex.ResultsAfter vitC treatment, the MAP (170 ± 4 vs. 133 ± 6 mm Hg; P < 0.05) and rSNA (161 ± 5 vs. 118 ± 12 spikes/s; P < 0.05) were significantly reduced only in the 2K-1C group. VitC improved the baroreflex control of heart rate (HR) and rSNA. The expression of AT1R, p47phox, and gp91phox was elevated (51, 184, and 132%, respectively) in the clipped kidney of 2K-1C group. VitC downregulated AT1R in the clipped kidney (31%). Catalase (CAT) expression was reduced in clipped (70%) and nonclipped (83%) kidneys of 2K-1C rats. VitC treatment augmented the expression of glutathione peroxidase (GPx) in both clipped (185%) and nonclipped (212%) kidneys of the 2K-1C group.ConclusionsThe present study suggests a role for oxidative stress in the cardiovascular and sympathetic alterations in renovascular hypertension, associated with changes in the expression of AT1R, NAD(P)H oxidase subunits, and antioxidant enzymes in the kidney.American Journal of Hypertension 2010; doi:10.1038/ajh.2010.11 [ABSTRACT FROM AUTHOR]

Background: We hypothesized that upregulation of angiotensin type 1 receptor (AT(1)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.