Effects of angiotensin converting enzyme inhibitor and angiotensin II type 1 receptor blocker on cardiac dysfunction induced by isoproterenol in dogs

J Cardiovasc Pharmacol. 2001 Oct:38 Suppl 1:S63-7. doi: 10.1097/00005344-200110001-00014.

Abstract

We examined whether angiotensin converting enzyme (ACE) inhibitors and angiotensin II type 1 receptor blockers (ARB) prevent isoproterenol (ISO)-induced left ventricular (LV) dysfunction in dogs. The effects of a large dose of ISO, 1 microg/kg/min, 3 h infusion, were investigated in three groups with simultaneous infusion of an ACE inhibitor (quinaprilat), ARB (candesartan) or saline. ISO infusion significantly decreased LV dP/dt, LV ejection fraction and LV fractional shortening, and significantly increased tau, the time constant of isovolume relaxation of LV, and LV end diastolic pressure. All of these changes were significantly attenuated in both the ACE inhibitor and ARB groups, especially in the ARB group. Serum levels of creatinin kinase isoform MB, lactate dehydrogenase and lipid peroxide were significantly increased by ISO. However, the increases in these markers of myocardial damage were significantly diminished by simultaneous infusion of an ACE inhibitor or ARB, especially by ARB. In conclusion, an ACE inhibitor and ARB prevent LV systolic and diastolic dysfunction as well as myocardial damage induced by excess beta-adrenergic stimulation.

MeSH terms

  • Adrenergic beta-Agonists / administration & dosage
  • Angiotensin II / blood
  • Angiotensin II / metabolism*
  • Angiotensin Receptor Antagonists*
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Creatine Kinase / blood
  • Creatine Kinase, MB Form
  • Dogs
  • Female
  • Heart Diseases / chemically induced*
  • Heart Diseases / drug therapy
  • Heart Diseases / prevention & control*
  • Hemodynamics / drug effects
  • Isoenzymes / blood
  • Isoproterenol / administration & dosage*
  • L-Lactate Dehydrogenase / blood
  • Lipid Peroxides / blood
  • Male
  • Receptor, Angiotensin, Type 1
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / prevention & control*

Substances

  • Adrenergic beta-Agonists
  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Isoenzymes
  • Lipid Peroxides
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • L-Lactate Dehydrogenase
  • Creatine Kinase
  • Creatine Kinase, MB Form
  • Isoproterenol