title: Hemodynamic, morphometric and autonomic patterns in hypertensive rats - Renin-Angiotensin system modulation.
abstract: BACKGROUND
  Spontaneously hypertensive rats develop left ventricular hypertrophy, increased blood pressure and blood pressure variability, which are important determinants of heart damage, like the activation of renin-angiotensin system.
  
  
  OBJECTIVE
  To investigate the effects of the time-course of hypertension over 1) hemodynamic and autonomic patterns (blood pressure; blood pressure variability; heart rate); 2) left ventricular hypertrophy; and 3) local and systemic Renin-angiotensin system of the spontaneously hypertensive rats.
  
  
  METHODS
  MALE SPONTANEOUSLY HYPERTENSIVE RATS WERE RANDOMIZED INTO TWO GROUPS: young (n=13) and adult (n=12). Hemodynamic signals (blood pressure, heart rate), blood pressure variability (BPV) and spectral analysis of the autonomic components of blood pressure were analyzed. LEFT ventricular hypertrophy was measured by the ratio of LV mass to body weight (mg/g), by myocyte diameter (mum) and by relative fibrosis area (RFA, %). ACE and ACE2 activities were measured by fluorometry (UF/min), and plasma renin activity (PRA) was assessed by a radioimmunoassay (ng/mL/h). Cardiac gene expressions of Agt, Ace and Ace2 were quantified by RT-PCR (AU).
  
  
  RESULTS
  The time-course of hypertension in spontaneously hypertensive rats increased BPV and reduced the alpha index in adult spontaneously hypertensive rats. Adult rats showed increases in left ventricular hypertrophy and in RFA. Compared to young spontaneously hypertensive rats, adult spontaneously hypertensive rats had lower cardiac ACE and ACE2 activities, and high levels of PRA. No change was observed in gene expression of Renin-angiotensin system components.
  
  
  CONCLUSIONS
  The observed autonomic dysfunction and modulation of Renin-angiotensin system activity are contributing factors to end-organ damage in hypertension and could be interacting. Our findings suggest that the management of hypertensive disease must start before blood pressure reaches the highest stable levels and the consequent established end-organ damage is reached.
authors.affiliation: Nephrology Department, Federal University of São Paulo - São Paulo/SP, Brazil. nanda.zamo@terra.com.br
authors.forename: Fernanda S
authors.initials: FS
authors.lastname: Zamo
authors.forename: Silvia
authors.initials: S
authors.lastname: Lacchini
authors.forename: Cristiano
authors.initials: C
authors.lastname: Mostarda
authors.forename: Silvana
authors.initials: S
authors.lastname: Chiavegatto
authors.forename: Ivana C M
authors.initials: IC
authors.lastname: Silva
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: Oliveira
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Irigoyen
mesh_terms: D000367:Age Factors; D000085962:Angiotensin-Converting Enzyme 2; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000502:physiology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000502:physiology*
chemical_list: D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2