title: Long-term effect of a chronic low-protein multideficient diet on the heart: Hypertension and heart failure in chronically malnourished young adult rats.
abstract: BACKGROUND
  We investigated whether a chronic low-protein multideficient diet (BRD) from weaning turns on cardiovascular adaptive responses that could culminate in hypertension and heart failure.
  
  
  RESULTS
  Systolic pressure (SP) and heart rate (HR) were determined in CTRL (normal diet) and BRD rats. Plasma albumin, plasma urea and urinary urea excretion decreased in BRD rats. In this group, echocardiography and the Langendorff technique showed: (i) increased HR and hypertension; (ii) decreased LVDP, dP/dtmax, dP/dtmin, cardiac output, ejection fraction, stroke volume and left ventricular diameter. BRD rats were less sensitive to isoproterenol (ISO) in LVDP and dP/dtmax, with unchanged dP/dtmin; Pressure-volume relationships indicated left-oriented shifts in LVDP, SP and DP, and decreased capacitance compared to CTRL. BRD rats had higher cardiac and lung indexes, accompanied by muscle atrophy and recent ventricular-infarcted areas, higher ventricular β1-AR content, and decreased β2-AR and α1-AR. Propranolol treatment gave similar ISO responses in both groups, disappearance of the infarcted regions and, except for β2-AR, recovery of normal receptor expression. BRD rats had intense stimulation of plasma membrane Ca2+-ATPase (PMCA) activity, with increased Ca2+affinity and inhibition of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA). Ventricular phospholamban increased and Na+/Ca2+exchanger decreased. PMCA activity correlated with an increase in its PKC-mediated phosphorylation, overlying a decrease in PKA-catalyzed phosphorylation. Propranolol normalized PKC and PKA activities with recovery of PMCA but not SERCA.
  
  
  CONCLUSIONS
  BRD triggers sympathetic exacerbation and dysfunction in Ca2+handling, accompanied by early onset of hypertension and left ventricle congestive heart failure.
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luiza V P
authors.initials: LVP
authors.lastname: Mendes
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sabrina R
authors.initials: SR
authors.lastname: Gonsalez
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Leonardo M
authors.initials: LM
authors.lastname: Oliveira-Pinto
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Amaury
authors.initials: A
authors.lastname: Pereira-Acácio
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Takiya
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging-INBEB, Brazil.
authors.forename: José H M
authors.initials: JHM
authors.lastname: Nascimento
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging-INBEB, Brazil.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Einicker-Lamas
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging-INBEB, Brazil; National Center of Structural Biology and Bioimaging-CENABIO, Federal University of Rio de Janeiro, Brazil; National Institute of Science and Technology for Regenerative Medicine, Brazil; Graduate Program in Translational Biomedicine, Grande Rio University, Duque de Caxias, Brazil.
authors.forename: Adalberto
authors.initials: A
authors.lastname: Vieyra
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Valéria M N
authors.initials: VMN
authors.lastname: Cunha
authors.affiliation: Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; National Institute of Science and Technology for Structural Biology and Bioimaging-INBEB, Brazil; National Center of Structural Biology and Bioimaging-CENABIO, Federal University of Rio de Janeiro, Brazil; National Institute of Science and Technology for Regenerative Medicine, Brazil. Electronic address: lara@icb.ufrj.br.
authors.forename: Lucienne S
authors.initials: LS
authors.lastname: Lara
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D002908:Chronic Disease; D018753:Diet, Protein-Restricted / Q000009:adverse effects* / Q000639:trends; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D044342:Malnutrition / Q000378:metabolism* / Q000473:pathology; D011488:Protein Deficiency / Q000378:metabolism* / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014508:Urea / Q000378:metabolism
chemical_list: D014508:Urea; D011494:Protein Kinases
keywords: Adrenergic receptors; Ca(2+) handling; Chronic undernutrition; Propranolol treatment; Protein kinases; Ventricular dysfunction