Inotropic effects of α1-adrenergic agonists in myocardium from rats with postinfarction heart failure

S. E. Litwin, D. E. Vatner, J. P. Morgan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In clinical and experimental heart failure, the inotropic response to β- adrenergic receptor stimulation is depressed. Therefore, non-β-adrenergic mechanisms may assume increasing importance for summoning inotropic reserve in the failing heart. To test the integrity of the inotropic pathway mediated by α1-adrenergic receptor stimulation in a model of chronic ischemic heart failure, we administered phenylephrine to noninfarcted left ventricular papillary muscles isolated from sham-operated rats (n = 10) and rats with large (> 40% left ventricular circumference) anterior myocardial infarctions (n = 9). Isometric force was monitored, and intracellular Ca2+ (Ca(i)/2+) transients were recorded with the bioluminescent protein aequorin. Compared with muscles from sham-operated rats, contractility of muscles from rats with postinfarction heart failure was depressed at extracellular Ca2+ concentrations between 0.5 and 3.0 mM. Phenylephrine produced comparable dose-dependent increases in developed tension (126 ± 4 vs. 125 ± 7% of baseline) and peak rate of tension rise (125 ± 4 vs. 140 ± 9% of baseline) in muscles from sham and infarcted rats, respectively. There was no significant change in the time course of the isometric twitch or in the time course or amplitude of the Ca(i)/2+ transient after phenylephrine administration in muscles from either group. No evidence of Ca(i)/2+ overload, as defined by spontaneous Ca2+ release, was observed during phenylephrine administration in muscles from normal or failing hearts. The density of α1-adrenoceptors measured with [3H]prazosin binding in crude membranes isolated from noninfarcted left ventricular tissue was not different in control and infarcted hearts (48 ± 5 vs. 53 ± 4 fmol/mg protein). These data indicate that the positive inotropic effect of α- agonists may he preserved in chronic ischemic heart failure. In both normal and failing myocardium, the inotropic effects of α1-adrenergic stimulation occurred with little or no increase in Ca(i)/2+ availability and no apparent adverse effects on myocardial relaxation. Therefore, agents that act by similar mechanisms may have certain therapeutic advantages over traditional inotropic agents in patients with heart failure.

Original languageEnglish (US)
Pages (from-to)H1553-H1563
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number5 38-5
DOIs
StatePublished - 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • calcium
  • myocardial contraction
  • myocardial infarction
  • α-adrenergic receptors

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