Sympathectomy or doxazosin, but not propranolol, blunt myocardial interstitial fibrosis in pressure-overload hypertrophy

Stefano Perlini, Giuseppina Palladini, Ivana Ferrero, Rossana Tozzi, Silvia Fallarini, Angelica Facoetti, Rosanna Nano, Francesca Clari, Giuseppe Busca, Roberto Fogari, Alberto U. Ferrari

Research output: Contribution to journalArticlepeer-review

Abstract

The adaptive changes that develop in the pressure-overloaded left ventricular (LV) myocardium include cardiomyocyte hypertrophy and interstitial fibrosis. Although the former is known to depend to a sizeable extent on sympathetic (over)activity, little information exists whether the same applies to the latter, ie, whether excess catecholamine exposure contributes to the imbalance between collagen deposition by fibroblasts and degradation by matrix metalloproteases (MMPs), eventually leading to LV collagen accumulation. Sprague-Dawley rats were subjected to abdominal aortic banding (B) or sham operation (S) and treated with β-blockade (Bb, oral propranolol, 40 mg/kg per day), chemical sympathectomy (Sx, 6-hydroxydopamine, 150 mg/kg intraperitoneal twice per week) or vehicle (Vh). Ten weeks later, systolic blood pressure, LV weight, collagen abundance (computer-aided histology), zymographic matrix metalloproteinase (MMP)-2 activity and its specific tissue inhibitor concentration (TIMP-2) were measured. Both sympathectomy and β-blockade failed to attenuate the banding-induced blood pressure elevation but significantly attenuated the attendant LV hypertrophy. As expected, pressure-overload hypertrophy was associated with interstitial fibrosis (collagen: 4.37plusmn;1.23% BVh versus 1.23±0.44% SVh, P

Original languageEnglish
Pages (from-to)1213-1218
Number of pages6
JournalHypertension
Volume46
Issue number5
DOIs
Publication statusPublished - Nov 2005

Keywords

  • Collagen
  • Extracellular matrix
  • Fibrosis
  • Heart failure
  • Hypertrophy
  • Sympathectomy

ASJC Scopus subject areas

  • Internal Medicine

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