Mechanism of negative lusitropic effect of α1-adrenoceptor stimulation in cat papillary muscles

Martín Vila-Petroff, Gustavo N. Pérez, Bernardo Alvarez, Horacio E. Cingolani, Alicia Mattiazzi

Research output: Contribution to journalArticle

Abstract

Experiments were performed in cat papillary muscles to explore the mechanisms by which α1-adrenoceptor stimulation affects myocardial relaxation. Phenylephrine (PE; 10 μM) + atenolol (1 μM; n = 8 experiments) produced a negative lusitropic effect, i.e., a prolongation of half- relaxation time (t(1/2); time to 50% relaxation) by 30 ± 10% (P <0.05) and a proportionally smaller increase in maximal velocity of relaxation (-Ṫ) than in maximal velocity of contraction (+Ṫ), which significantly increased the ratio +Ṫ/-Ṫ. A similar increase in contractility, produced by increasing calcium, failed to significantly change t(1/2) and +Ṫ/-Ṫ. PE- induced negative lusitropic effect was significantly inhibited by two protein kinase C (PKC) inhibitors, staurosporine (0.1 μM) and chelerythrine (10 μM). 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 μM). 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 α1-adrenoceptor stimulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume270
Issue number2 39-2
StatePublished - 1996
Externally publishedYes

Fingerprint

Alkalosis
Sodium-Hydrogen Antiporter
Papillary Muscles
Adrenergic Receptors
Protein Kinase C
Cats
Calcium
Atenolol
Staurosporine
Protein C Inhibitor
Myofibrils
Phenylephrine
Protein Kinase Inhibitors
Fluorescent Dyes
chelerythrine
ethylisopropylamiloride
2-(2-(2-chloro-3-(2-(3,3-dimethyl-5-sulfo-1-(4-sulfo-butyl)-3H-indol-2-yl)-vinyl)-cyclohex-2-enylidene)-ethylidene)-3,3-dimethyl-1-(4-sulfo-butyl)-2,3-dihydro-1H-indole-5-carboxylic acid
6-carboxyfluorescein

Keywords

  • intracellular alkalosis
  • myocardial relaxation
  • protein kinase C inhibitors
  • sodium/hydrogen exchanger

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Mechanism of negative lusitropic effect of α1-adrenoceptor stimulation in cat papillary muscles. / Vila-Petroff, Martín; Pérez, Gustavo N.; Alvarez, Bernardo; Cingolani, Horacio E.; Mattiazzi, Alicia.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 270, No. 2 39-2, 1996.

Research output: Contribution to journalArticle

Vila-Petroff, Martín ; Pérez, Gustavo N. ; Alvarez, Bernardo ; Cingolani, Horacio E. ; Mattiazzi, Alicia. / Mechanism of negative lusitropic effect of α1-adrenoceptor stimulation in cat papillary muscles. In: American Journal of Physiology - Heart and Circulatory Physiology. 1996 ; Vol. 270, No. 2 39-2.
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