title: Upregulation of AT1R and iNOS in the rostral ventrolateral medulla (RVLM) is essential for the sympathetic hyperactivity and hypertension in the 2K-1C Wistar rat model.
abstract: 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.
authors.affiliation: Cardiovascular Division, Department of Physiology, Federal University of Sao Paulo, São Paulo, Brazil.
authors.forename: Elizabeth Barbosa
authors.initials: EB
authors.lastname: de Oliveira-Sales
authors.forename: Erika Emy
authors.initials: EE
authors.lastname: Nishi
authors.forename: Mirian Aparecida
authors.initials: MA
authors.lastname: Boim
authors.forename: Miriam Sterman
authors.initials: MS
authors.lastname: Dolnikoff
authors.forename: Cássia T
authors.initials: CT
authors.lastname: Bergamaschi
authors.forename: Ruy R
authors.initials: RR
authors.lastname: Campos
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015870:Gene Expression; D006146:Guanidines / Q000008:administration & dosage; D006978:Hypertension, Renovascular / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D044140:Receptor, Angiotensin, Type 1; D052247:Nitric Oxide Synthase Type II; C004479:pimagedine