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. Papp, L. Szekeres

Research output: Contribution to journalArticle

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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 2003

Fingerprint

Animal Models
Endothelin-1
Exercise Test
Blood Pressure
Cardiac Arrhythmias
Calcium Channel Blockers
Ventricular Pressure
pranidipine
Vasopressins
Pharmaceutical Preparations
Adrenergic Receptors
Electrocardiography
Ischemia
Heart Rate
Dogs
Rabbits

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

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

Acute and chronic anti-ischemic actions of pranidipine in three animal models. / Takase, H.; Kovanecz, I.; Mori, T.; Ohura, M.; Fujiki, H.; Yoshida, K.; Sumida, T.; Tominaga, M.; Papp, J.; Szekeres, L.

In: Asia Pacific Journal of Pharmacology, Vol. 16, No. 1, 03.2003, p. 29-37.

Research output: Contribution to journalArticle

Takase, H, Kovanecz, I, Mori, T, Ohura, M, Fujiki, H, Yoshida, K, Sumida, T, Tominaga, M, Papp, J & Szekeres, L 2003, 'Acute and chronic anti-ischemic actions of pranidipine in three animal models', Asia Pacific Journal of Pharmacology, vol. 16, no. 1, pp. 29-37.
Takase H, Kovanecz I, Mori T, Ohura M, Fujiki H, Yoshida K et al. Acute and chronic anti-ischemic actions of pranidipine in three animal models. Asia Pacific Journal of Pharmacology. 2003 Mar;16(1):29-37.
Takase, H. ; Kovanecz, I. ; Mori, T. ; Ohura, M. ; Fujiki, H. ; Yoshida, K. ; Sumida, T. ; Tominaga, M. ; Papp, J. ; Szekeres, L. / Acute and chronic anti-ischemic actions of pranidipine in three animal models. In: Asia Pacific Journal of Pharmacology. 2003 ; Vol. 16, No. 1. pp. 29-37.
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