Acute and chronic anti-ischemic actions of pranidipine in three animal models

H. Takase, I. Kovanecz, T. Mori, M. Ohura, H. Fujiki, K. Yoshida, T. Sumida, M. Tominaga, J. G. Papp, L. Szekeres

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Abstract

The acute and chronic effects of pranidipine, a long-acting calcium channel blocker, were examined in three models of cardiac ischemia. In anesthetized dogs, an intracoronary endothelin-1 (ET-1) decreased coronary blood flow (CBF) and maximal first derivative of left ventricular pressure (LVdP/dt max), increased left ventricular end-diastolic pressure (LVEDP), and caused ST change and arrhythmias. When pranidipine (1 and 3 μg/kg i.v.) was injected 10 min before the ET-1 challenge, pranidipine, by itself, increased CBF dose-dependently and depressed the ET-1-induced changes in CBF, LVEDP, ST-segment, and arrhythmias. Vasopressin evoked a depression in the ST-segment of lead II electrocardiogram in Donryu rats. Pretreatment with pranidipine (10 and 30 μg/kg i.v.) significantly inhibited the ST depression. In chronically instrumented conscious rabbits, the baseline values of LVEDP, heart rate, and ST-segment in endocardial electrogram and their changes by a reproducible standardized "test" stress (combined application of α- and β-adrenoceptor agonists) were recorded at the start and 3 hr after drug administration. Pranidipine (1 mg/kg p.o.) and its vehicle were administered once daily for 1 week; the baseline values and changes secondary to the "test" stress were recorded on the first, third, fifth, and seventh days. Pranidipine did not affect the baseline values but significantly reduced the ST-segment and LVEDP elevation by the "test" stress. Repeated administration of the drug over a 1-week period did not affect the degree of protection or the level of the baseline values. Taken together, we conclude that pranidipine represents an orally effective anti-ischemic agent.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalAsia Pacific Journal of Pharmacology
Volume16
Issue number1
Publication statusPublished - Mar 1 2003

Keywords

  • "Test" stress
  • Anti-ischemic
  • Arginine vasopressin
  • Coronary blood flow
  • Endothelin-1
  • Pranidipine

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Takase, H., Kovanecz, I., Mori, T., Ohura, M., Fujiki, H., Yoshida, K., Sumida, T., Tominaga, M., Papp, J. G., & Szekeres, L. (2003). Acute and chronic anti-ischemic actions of pranidipine in three animal models. Asia Pacific Journal of Pharmacology, 16(1), 29-37.