Effects of carvedilol or amlodipine on target organ damage in L-NAME hypertensive rats: their relationship with blood pressure variability

J Am Soc Hypertens. 2017 Apr;11(4):227-240. doi: 10.1016/j.jash.2017.02.007. Epub 2017 Mar 2.

Abstract

The aim of the study was to compare the effects of chronic oral treatment with carvedilol or amlodipine on blood pressure, blood pressure variability and target organ damage in N-nitro-l-arginine methyl ester (L-NAME) hypertensive rats. Wistar rats were treated with L-NAME administered in the drinking water for 8 weeks together with oral administration of carvedilol 30 mg/kg (n = 6), amlodipine 10 mg/kg (n = 6), or vehicle (n = 6). At the end of the treatment, echocardiographic evaluation, blood pressure, and short-term variability measurements were performed. Left ventricular and thoracic aortas were removed to assess activity of metalloproteinase 2 and 9 and expression levels of transforming growth factor β, tumor necrosis factor α, and interleukin 6. Histological samples were prepared from both tissues. Carvedilol and amlodipine induced a comparable reduction of systolic and mean arterial pressure and its short-term variability in L-NAME rats. The expression of transforming growth factor β, tumor necrosis factor α, and interleukin 6 decreased in both organs after carvedilol or amlodipine treatment and the activity of metalloproteinase was reduced in aortic tissue. Treatment with carvedilol or amlodipine completely prevented left ventricular collagen deposition and morphometric alterations in aorta. Oral chronic treatment with carvedilol or amlodipine significantly attenuates blood pressure variability and reduces target organ damage and biomarkers of tissue fibrosis and inflammation in L-NAME hypertensive rats.

Keywords: calcium channel blocker; left ventricle; thoracic aorta; β-blocker.

Publication types

  • Comparative Study

MeSH terms

  • Amlodipine / pharmacology
  • Amlodipine / therapeutic use
  • Animals
  • Antihypertensive Agents / pharmacology*
  • Antihypertensive Agents / therapeutic use
  • Aorta / drug effects*
  • Aorta / pathology*
  • Biomarkers / metabolism
  • Blood Pressure / drug effects
  • Blood Pressure Determination
  • Carbazoles / pharmacology
  • Carbazoles / therapeutic use
  • Carvedilol
  • Collagen / metabolism
  • Disease Models, Animal
  • Fibrosis
  • Heart Ventricles / drug effects*
  • Heart Ventricles / pathology*
  • Humans
  • Hypertension / chemically induced
  • Hypertension / drug therapy*
  • Interleukin-6 / metabolism
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NG-Nitroarginine Methyl Ester / toxicity
  • Propanolamines / pharmacology
  • Propanolamines / therapeutic use
  • Rats
  • Rats, Wistar
  • Transforming Growth Factor beta / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Carbazoles
  • Interleukin-6
  • Propanolamines
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Carvedilol
  • Amlodipine
  • Collagen
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat
  • NG-Nitroarginine Methyl Ester