title: Vascular alterations during the development and progression of experimental heart failure.
abstract: BACKGROUND
  Congestive heart failure (HF) is a multifactorial and progressive condition associated with multiple systemic and vascular alterations. The onset and progression of these alterations and the cause of the condition remain undefined. The main purpose of the present study was to help understand the temporal evolution of vascular alterations and their contribution to the pathogenesis of HF. Vascular reactivity to angiotensin II (Ang II) and norepinephrine (NE), as well as circulating and local angiotensin-converting enzyme (ACE) activity, were assessed in the Syrian cardiomyopathic hamster (SCH) model.
  
  
  RESULTS
  We have shown previously that in 2-month-old SCH animals that had not yet developed the clinical manifestations of HF, the contractile response of aortic rings to Ang II was markedly enhanced compared with normal animals. In addition, SCHs showed increased ACE activity in aortic tissue. To assess the relevance of these findings to the development and progression of HF, the temporal evolution of the contractile response of aortic rings to Ang II and NE was evaluated in hamsters at 2, 6, and 11 months of age. Age-matched normal hamsters were used as controls. Within the SCH group, the maximal contraction induced to 10 mumol/L of NE in 2- and 11-month-old animals was similar, but significantly greater than in the age-matched controls (for 2-month-old animals; 1.43 +/- 0.21 g in SCHs v 1.04 +/- 0.15 g in controls; P < .05 and for 11-month-old animals; 1.41 +/- 0.14 g in SCHs v 1.06 +/- 0.07 g in controls; P < .05). The drug concentrations necessary to obtain 50% of the maximal response from the NE concentration-response curves were similar for SCHs and controls at all ages tested. In contrast, the contractility induced by 0.1 mumol/L of Ang II increased progressively in cardiomyopathic animals from 2 to 11 months of age (from 1.3 +/- 0.1 to 1.8 +/- 0.2 g; n = 9; P < .05). In age-matched normal hamsters, the contractile response to Ang II (0.9 +/- 0.1 g) did not vary with age. These findings were observed concomitantly with an increased ACE activity in plasma (18.65 +/- 1.77 nmol/mg x min in controls v 26.5 +/- 1.79 nmol/mg x min in SCHs; P < .05; n = 7) and in heart tissue (0.244 +/- 0.016 nmol/mg x min in controls v 0.563 +/- 0.027 nmol/mg x min in SCHs; P < .05; n = 20) of 11-month-old SCHs.
  
  
  CONCLUSIONS
  These results suggest that, in young animals, increased vascular response to elevated levels of NE and hyperreactivity to Ang II could be critical factors in the development and progression of HF. Indeed, Ang II-induced contractility, as well as plasma and heart ACE activity, are good predictors of the progression and severity of HF.
authors: Department of Pharmacology, University of Puerto Rico-School of Medicine, San Juan 00936-5067.
authors: M J
authors: MJ
authors: Crespo
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006224:Cricetinae; D004195:Disease Models, Animal; D018450:Disease Progression; D006333:Heart Failure / Q000503:physiopathology*; D008297:Male; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009638:Norepinephrine