Nebivolol prevents myocardial fibrosis and diastolic dysfunction in salt-loaded spontaneously hypertensive rats

J Am Soc Hypertens. 2012 Sep-Oct;6(5):316-23. doi: 10.1016/j.jash.2012.06.001.

Abstract

Background: We have demonstrated previously that a high-salt diet (HS) produces myocardial fibrosis, left ventricular (LV) dysfunction, and renal insufficiency in adult spontaneously hypertensive rats (SHR), and that blockade of the renin-angiotensin system prevented those adverse effects of HS.

Methods and results: Eight-week-old male SHR were divided into four groups: controls received regular rat chow (0.6 NaCl); the other three were given HS. The second group was given placebo; the third, nebivolol (2 × 10 mg/kg/day) orally; and, the fourth, the same dose of nebivolol by osmotic minipump. Rats received respective treatments for 8 weeks. The data demonstrated that the HS induced increased cardiac mass (2.85 ± 0.05 vs. 5.36 ± 0.22 mg/g; P < .05 in control and HS groups, respectively); LV fibrosis as indicated by higher hydroxyproline concentration; further increase in arterial pressure (161 ± 7 vs. 184 ± 8 mm Hg; P < .05); myocardial ischemia; and LV diastolic dysfunction. Nebivolol ameliorated the adverse cardiac effects of HS, demonstrated by decreased LV mass and fibrosis and improved coronary hemodynamics and LV function.

Conclusions: The effects of nebivolol were independent of arterial pressure. The results of this study provide important laboratory data that support a rationale for nebivolol in the treatment of patients with hypertension having diastolic dysfunction with preserved ejection fraction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenergic beta-1 Receptor Antagonists / administration & dosage
  • Adrenergic beta-1 Receptor Antagonists / pharmacokinetics
  • Animals
  • Benzopyrans* / administration & dosage
  • Benzopyrans* / pharmacokinetics
  • Biological Availability
  • Blood Pressure / drug effects*
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / pharmacokinetics
  • Ethanolamines* / administration & dosage
  • Ethanolamines* / pharmacokinetics
  • Fibrosis / chemically induced
  • Fibrosis / metabolism
  • Fibrosis / prevention & control
  • Hemodynamics
  • Humans
  • Hydroxyproline / metabolism
  • Infusion Pumps
  • Injections / methods
  • Models, Animal
  • Myocardial Contraction / drug effects*
  • Myocardial Ischemia / chemically induced
  • Myocardial Ischemia / prevention & control
  • Myocardium* / metabolism
  • Myocardium* / pathology
  • Nebivolol
  • Rats
  • Rats, Inbred SHR
  • Sodium Chloride, Dietary* / administration & dosage
  • Sodium Chloride, Dietary* / adverse effects
  • Sodium Chloride, Dietary* / pharmacokinetics
  • Ventricular Dysfunction, Left* / chemically induced
  • Ventricular Dysfunction, Left* / metabolism
  • Ventricular Dysfunction, Left* / prevention & control

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Benzopyrans
  • Cardiotonic Agents
  • Ethanolamines
  • Sodium Chloride, Dietary
  • Nebivolol
  • Hydroxyproline