Mechanism of negative lusitropic effect of alpha 1-adrenoceptor stimulation in cat papillary muscles.

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    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 0370511 Publication Model: Print Cited Medium: Print ISSN: 0002-9513 (Print) Linking ISSN: 00029513 NLM ISO Abbreviation: Am J Physiol Subsets: MEDLINE
    • Publication Information:
      Publication: Bethesda, MD : American Physiological Society
      Original Publication: Washington [etc.] American Physiological Society.
    • Subject Terms:
      Myocardial Contraction/*physiology ; Papillary Muscles/*physiology ; Receptors, Adrenergic, alpha/*physiology; Actin Cytoskeleton/metabolism ; Amiloride/analogs & derivatives ; Amiloride/pharmacology ; Animals ; Anti-Arrhythmia Agents/pharmacology ; Calcium/metabolism ; Cats ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Intracellular Membranes/metabolism ; Phenylephrine/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Protein Kinase C/physiology ; Receptors, Adrenergic, alpha/drug effects
    • Abstract:
      Experiments were performed in cat papillary muscles to explore the mechanisms by which alpha 1-adrenoceptor stimulation affects myocardial relaxation. Phenylephrine (PE; 10 microM) + atenolol (1 microM; n = 8 experiments) produced a negative lusitropic effect, i.e., a prolongation of half-relaxation time (t1/2; time to 50% relaxation) by 30 +/- 10% (P < 0.05) and a proportionally smaller increase in maximal velocity of relaxation (-T) than in maximal velocity of contraction (+T), which significantly increased the ratio +T/-T. A similar increase in contractility, produced by increasing calcium, failed to significantly change t1/2 and +T/-T. PE-induced negative lusitropic effect was significantly inhibited by two protein kinase C (PKC) inhibitors, staurosporine (0.1 microM) and chelerythrine (10 microM). PE also increased intracellular pH by 0.18 +/- 0.05 pH units (P < 0.05, n = 4), as measured by the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Intracellular alkalosis and the negative lusitropic effect of PE were prevented by the Na+/H+ exchanger inhibitor ethylisopropylamiloride (10 microM). No significant changes in calcium myofilament sensitivity and maximal tension were detected in trabeculae treated with PE either before or after chemical skinning. These results indicate that a Na+/H+ exchanger-induced intracellular alkalosis, possibly mediated by PKC activation, may fully account for the negative lusitropism of alpha 1-adrenoceptor stimulation.
    • Accession Number:
      0 (Anti-Arrhythmia Agents)
      0 (Receptors, Adrenergic, alpha)
      1WS297W6MV (Phenylephrine)
      7DZO8EB0Z3 (Amiloride)
      EC 2.7.11.13 (Protein Kinase C)
      SY7Q814VUP (Calcium)
      VW50CE070T (ethylisopropylamiloride)
    • Publication Date:
      Date Created: 19960201 Date Completed: 19961220 Latest Revision: 20171213
    • Publication Date:
      20250114
    • Accession Number:
      10.1152/ajpheart.1996.270.2.H701
    • Accession Number:
      8779848