title: Sex Hormones Promote Opposite Effects on ACE and ACE2 Activity, Hypertrophy and Cardiac Contractility in Spontaneously Hypertensive Rats.
abstract: There is growing interest in sex differences and RAS components. However, whether gender influences cardiac angiotensin I-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity is still unknown. In the present work, we determined the relationship between ACE and ACE2 activity, left ventricular function and gender in spontaneously hypertensive rats (SHRs).
  
  
  
  Twelve-week-old female (F) and male (M) SHRs were divided into 2 experimental groups (n = 7 in each group): sham (S) and gonadectomized (G). Fifty days after gonadectomy, we measured positive and negative first derivatives (dP/dt maximum left ventricle (LV) and dP/dt minimum LV, respectively), hypertrophy (morphometric analysis) and ACE and ACE2 catalytic activity (fluorimetrically). Expression of calcium handling proteins was measured by western blot. Male rats exhibited higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. Orchiectomy decreased the activity of these enzymes and hypertrophy, while ovariectomy increased hypertrophy and ACE2, but did not change ACE activity. For cardiac function, the male sham group had a lower +dP/dt than the female sham group. After gonadectomy, the +dP/dt increased in males and reduced in females. The male sham group had a lower -dP/dt than the female group. After gonadectomy, the -dP/dt increased in the male and decreased in the female groups when compared to the sham group. No difference was observed among the groups in SERCA2a protein expression. Gonadectomy increased protein expression of PLB (phospholamban) and the PLB to SERCA2a ratio in female rats, but did not change in male rats.
  
  
  
  Ovariectomy leads to increased cardiac hypertrophy, ACE2 activity, PLB expression and PLB to SERCA2a ratio, and worsening of hemodynamic variables, whereas in males the removal of testosterone has the opposite effects on RAS components.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: P L M
authors.initials: PL
authors.lastname: Dalpiaz
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: A Z
authors.initials: AZ
authors.lastname: Lamas
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: I F
authors.initials: IF
authors.lastname: Caliman
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: E H
authors.initials: EH
authors.lastname: Ribeiro
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: G R
authors.initials: GR
authors.lastname: Abreu
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Moyses
authors.affiliation: Department of Pharmacy, University Vila Velha, Vila Velha, Espirito Santo, Brazil.
authors.forename: T U
authors.initials: TU
authors.lastname: Andrade
authors.affiliation: Nucleus of Biotechnology, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: S A
authors.initials: SA
authors.lastname: Gouvea
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Alves
authors.affiliation: Department of Biophysics, Escola Paulista de Medicina, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: A K
authors.initials: AK
authors.lastname: Carmona
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: N S
authors.initials: NS
authors.lastname: Bissoli
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology*; D003720:Densitometry; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006066:Gonads / Q000187:drug effects / Q000601:surgery; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011918:Rats, Inbred SHR; D013599:Systole / Q000187:drug effects
chemical_list: D012739:Gonadal Steroid Hormones; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2