Effects of a pure alpha/beta-adrenergic receptor blocker on monocrotaline-induced pulmonary arterial hypertension with right ventricular hypertrophy in rats

Circ J. 2009 Dec;73(12):2337-41. doi: 10.1253/circj.cj-09-0213. Epub 2009 Oct 13.

Abstract

Background: It is unclear how much the sympathetic nervous system is involved in the development of pulmonary arterial hypertension (PAH). The present study examined whether or not a pure alpha/beta-adrenergic receptor blocker (arotinolol) could prevent the development of PAH and right ventricular hypertrophy (RVH) in a rat model of monocrotaline (MCT)-induced PAH.

Methods and results: The heart rate, arterial blood pressure (BP), left ventricular pressure, pulmonary artery pressure (PAP), and right ventricular pressure (RVP) were measured after administration of arotinolol or saline for 2 weeks. Ventricular weight and myocyte size were also measured. Mean PAP was increased less in the arotinolol group (n=6), (53 +/-9 vs 21 +/-2 mmHg in the control (n=6); P<0.01). Systolic RVP was also less in the arotinolol group (41 +/-3 vs 91 +/-14 mmHg in the control, P<0.05) without differences in BP. It also significantly reduced the RV/body weight ratio (0.58 +/-0.01 vs 0.77 +/-0.04 mg/g; P<0.01). Furthermore, the myocyte width was significantly decreased in the arotinolol group.

Conclusions: The pure alpha/beta-blocker arotinolol prevented the progression of MCT-induced PAH and RVH in rats, suggesting that sympathetic nervous activation might play a role in the development of PAH.

MeSH terms

  • Adrenergic alpha-Antagonists / pharmacology*
  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Blood Pressure / drug effects
  • Disease Models, Animal
  • Disease Progression
  • Heart Rate / drug effects
  • Hypertension, Pulmonary / chemically induced
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / pathology
  • Hypertension, Pulmonary / physiopathology
  • Hypertrophy, Right Ventricular / chemically induced
  • Hypertrophy, Right Ventricular / drug therapy*
  • Hypertrophy, Right Ventricular / pathology
  • Hypertrophy, Right Ventricular / physiopathology
  • Male
  • Monocrotaline
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / pathology
  • Propanolamines / pharmacology*
  • Rats
  • Rats, Wistar
  • Sympathetic Nervous System / drug effects*
  • Sympathetic Nervous System / physiopathology
  • Ventricular Pressure / drug effects

Substances

  • Adrenergic alpha-Antagonists
  • Adrenergic beta-Antagonists
  • Propanolamines
  • arotinolol
  • Monocrotaline