title: Aldosterone Contributes to Sympathoexcitation in Renovascular Hypertension.
abstract: BACKGROUND
  Although angiotensin II (Ang II) is essential to the development of renovascular hypertension, aldosterone plays a role as well. Recent studies have demonstrated a cross-talk between Ang II type 1 and mineralocorticoid receptors in the brain and kidneys. However, the role of aldosterone in the autonomic and renal dysfunction of renovascular hypertension is not well understood.
  
  
  OBJECTIVE
  The current study evaluated whether aldosterone contributes to cardiovascular and renal dysfunction in the 2 kidney-1 clip (2K1C) model.
  
  
  METHODS
  Mean arterial pressure (MAP) and baroreceptor reflex for control of the heart rate were evaluated in 2K1C treated or not treated with spironolactone (200mg/kg/day, 7 days). Tonic and reflex control of renal sympathetic nerve activity (rSNA) were assessed in urethane-anaesthetized rats. Plasma renin activity (PRA), kidney renin protein expression, renal injury, and central AT1 receptor protein expression were assessed.
  
  
  RESULTS
  Spiro reduced MAP (198±4 vs. 170±9mm Hg; P < 0.05), normalized rSNA (147±9 vs. 96±10 pps; P < 0.05), and increased renal baroreceptor reflex sensitivity in the 2K1C rats. Spiro reduced α-smooth muscle actin expression in the nonclipped kidney in the 2K1C group (5±0.6 vs. 1.1±0.2%; P < 0.05). There was no change in PRA; however, a decrease in renin protein expression in the nonclipped kidney was found in the 2K1C treated group (217±30 vs. 160±19%; P < 0.05). Spiro treatment decreased AT1 receptor in the central nervous system (CNS) only in 2K1C rats (138±10 vs. 84±12%; P < 0.05).
  
  
  CONCLUSIONS
  Aldosterone contributes to autonomic dysfunction and intrarenal injury in 2K1C, these effects are mediated by the CNS.
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Gisele S
authors: GS
authors: Lincevicius
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Caroline G
authors: CG
authors: Shimoura
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Erika E
authors: EE
authors: Nishi
authors: Department of Psychobiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Juliana C
authors: JC
authors: Perry
authors: Nephrology Division, Department of Medicine - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
authors: Dulce E
authors: DE
authors: Casarini
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Guiomar N
authors: GN
authors: Gomes
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil;
authors: Cássia T
authors: CT
authors: Bergamaschi
authors: Department of Physiology - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil; ruy.camposjr@unifesp.br.
authors: Ruy R
authors: RR
authors: Campos
mesh_terms: D000199:Actins / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D062186:Arterial Pressure; D017704:Baroreflex; D004195:Disease Models, Animal; D006339:Heart Rate; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects; D013148:Spironolactone / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D000199:Actins; D000450:Aldosterone; D000959:Antihypertensive Agents; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D012083:Renin; D013148:Spironolactone; C498862:Acta2 protein, rat
keywords: baroreflex dysfunction; blood pressure; hypertension; renal injury; renin–angiotensin–aldosterone; renovascular hypertension; sympathoexcitation.