Effects of angiotensin converting enzyme inhibition on crossbridge properties of diaphragm in cardiomyopathic hamsters of the dilated bio 53-58 strain

Am J Respir Crit Care Med. 1997 Feb;155(2):630-6. doi: 10.1164/ajrccm.155.2.9032205.

Abstract

Crossbridge properties of cardiomyopathic Syrian hamster (CSH) diaphragm from the dilated Bio 53-58 strain were analyzed after 5-mo of treatment with the angiotensin converting enzyme (ACE) inhibitor perindopril (1 mg/kg/d by oral gavage). Three groups were studied: control F1B hamsters (C; n = 14); CSH given placebo (PL; n = 11 ); and perindopril-treated CSH (PE; n = 11). Peak isometric tension was lower in PL than in C, in both twitch (21.4 +/- 1.5 versus 46.9 +/- 1.5 mN/mm2; p < 0.001) and tetanus (41.0 +/- 2.7 versus 90.5 +/- 3.3 mN/mm2; p < 0.001). In PE, peak isometric tension was intermediate between C and PL, and was significantly lower than in C and higher than in PL. The single force of one crossbridge (pi), the number (m) of crossbridges, the turnover rate of myosin adenosine triphosphatase (ATPase) (kcat), and peak mechanical efficiency (Effmax) were calculated from A.F. Huxley's equations; m was lower in PL than in C, in both twitch (3.4 +/- 0.2 versus 4.9 +/- 0.2 10(9)/mm2; p < 0.001) and tetanus (4.0 +/- 0.3 versus 8.9 +/- 0.7 10(9)/mm2; p < 0.001); m was higher in PE than in PL, in both twitch 4.3 +/- 0.5 versus 3.4 +/- 0.2 10(9)/mm2; NS) and tetanus (6.2 +/- 0.4 versus 4.0 +/- 0.3 10(9)/mm2; p < 0.01), with no change in pi. In the three groups, Effmax correlated linearly with kcat (r = 0.93; p = 0.001) and showed a negative linear correlation with pi (r = 0.996; p = 0.001). In conclusion, our results show that in experimental cardiomyopathy, ACE inhibitor mainly helps to prevent a decrease in the number of diaphragm muscle crossbridges, resulting in preserved peak isometric tension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Biomechanical Phenomena
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / physiopathology*
  • Cricetinae
  • Diaphragm / drug effects*
  • Diaphragm / metabolism
  • Diaphragm / physiology
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Indoles / pharmacology*
  • Isometric Contraction / drug effects
  • Mesocricetus
  • Peptidyl-Dipeptidase A / blood
  • Perindopril

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Indoles
  • Peptidyl-Dipeptidase A
  • Perindopril