Lercanidipine protects the heart from low-flow ischemia damage and antagonizes the vasopressor activity of endothelin-1

Giuseppe Rossoni, Micaela Bernareggi, V. D G Colonna, Gianluca Polvani, Ferruccio Berti

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Lercanidipine, a calcium-entry blocker of the dihydropyridine (DHP) family, and its two enantiomers were tested in perfused rabbit hearts subjected under electrical pacing to low-flow ischemia (40-min reduction of perfusion rate from 20 ml/min to 0.2 ml/min) and reperfusion. Lercanidipine infused for 5 min before flow rate reduction prevented in a dose-related manner the increase of the ischemic resting tension (ventricular contracture) and favored a graded recovery of cardiac contractility with regular pacing at reperfusion. These findings were also well correlated with the trends of coronary perfusion pressure (CPP) values which were preserved in the range of pre-ischemic values. Nitrendipine appears to be less potent than lercanidipine in reducing the ventricular contracture. The (S)-enantiomer of lercanidipine displayed a dose-dependent protective activity against acute ischemic myocardial contracture on the same order of potency of the racemic lercanidipine. The (R)-enantiomer of lercanidipine was devoid of anti- ischemic activity. In these experiments lercanidipine did not modify the rate of prostacyclin release from the cardiac tissue, particularly at reperfusion. Lercanidipine shifted to the right the dose-response curve of endothelin-1 (ET-1) on CPP (DR = 1.88). Furthermore, the hyper-responsiveness of the coronary vasculature to ET-1 induced by infusing the hearts with N(G)- monomethyl-L-arginine was markedly reduced by lercanidipine. These data clearly indicate that lercanidipine has potent anti-ischemic activity in low- flow perfused rabbit hearts and suggest that this activity is mostly confined to the (S)-enantiomer of the racemic lercanidipine. Moreover, the ability of lercanidipine to control the vasopressor activity of ET-1 further stresses the usefulness of this class of compounds for treatment of essential hypertension and vasospastic angina.

Original languageEnglish
JournalJournal of Cardiovascular Pharmacology
Volume29
Issue numberSUPPL. 1
Publication statusPublished - 1997

Fingerprint

Endothelin-1
Ischemia
Reperfusion
Perfusion
Contracture
lercanidipine
Ischemic Contracture
Rabbits
Nitrendipine
Pressure
Epoprostenol
Arginine
Calcium

Keywords

  • Endothelin-1
  • Lercanidipine
  • Low-flow ischemia reperfusion
  • Prostacyclin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology

Cite this

Lercanidipine protects the heart from low-flow ischemia damage and antagonizes the vasopressor activity of endothelin-1. / Rossoni, Giuseppe; Bernareggi, Micaela; Colonna, V. D G; Polvani, Gianluca; Berti, Ferruccio.

In: Journal of Cardiovascular Pharmacology, Vol. 29, No. SUPPL. 1, 1997.

Research output: Contribution to journalArticle

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AU - Berti, Ferruccio

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N2 - Lercanidipine, a calcium-entry blocker of the dihydropyridine (DHP) family, and its two enantiomers were tested in perfused rabbit hearts subjected under electrical pacing to low-flow ischemia (40-min reduction of perfusion rate from 20 ml/min to 0.2 ml/min) and reperfusion. Lercanidipine infused for 5 min before flow rate reduction prevented in a dose-related manner the increase of the ischemic resting tension (ventricular contracture) and favored a graded recovery of cardiac contractility with regular pacing at reperfusion. These findings were also well correlated with the trends of coronary perfusion pressure (CPP) values which were preserved in the range of pre-ischemic values. Nitrendipine appears to be less potent than lercanidipine in reducing the ventricular contracture. The (S)-enantiomer of lercanidipine displayed a dose-dependent protective activity against acute ischemic myocardial contracture on the same order of potency of the racemic lercanidipine. The (R)-enantiomer of lercanidipine was devoid of anti- ischemic activity. In these experiments lercanidipine did not modify the rate of prostacyclin release from the cardiac tissue, particularly at reperfusion. Lercanidipine shifted to the right the dose-response curve of endothelin-1 (ET-1) on CPP (DR = 1.88). Furthermore, the hyper-responsiveness of the coronary vasculature to ET-1 induced by infusing the hearts with N(G)- monomethyl-L-arginine was markedly reduced by lercanidipine. These data clearly indicate that lercanidipine has potent anti-ischemic activity in low- flow perfused rabbit hearts and suggest that this activity is mostly confined to the (S)-enantiomer of the racemic lercanidipine. Moreover, the ability of lercanidipine to control the vasopressor activity of ET-1 further stresses the usefulness of this class of compounds for treatment of essential hypertension and vasospastic angina.

AB - Lercanidipine, a calcium-entry blocker of the dihydropyridine (DHP) family, and its two enantiomers were tested in perfused rabbit hearts subjected under electrical pacing to low-flow ischemia (40-min reduction of perfusion rate from 20 ml/min to 0.2 ml/min) and reperfusion. Lercanidipine infused for 5 min before flow rate reduction prevented in a dose-related manner the increase of the ischemic resting tension (ventricular contracture) and favored a graded recovery of cardiac contractility with regular pacing at reperfusion. These findings were also well correlated with the trends of coronary perfusion pressure (CPP) values which were preserved in the range of pre-ischemic values. Nitrendipine appears to be less potent than lercanidipine in reducing the ventricular contracture. The (S)-enantiomer of lercanidipine displayed a dose-dependent protective activity against acute ischemic myocardial contracture on the same order of potency of the racemic lercanidipine. The (R)-enantiomer of lercanidipine was devoid of anti- ischemic activity. In these experiments lercanidipine did not modify the rate of prostacyclin release from the cardiac tissue, particularly at reperfusion. Lercanidipine shifted to the right the dose-response curve of endothelin-1 (ET-1) on CPP (DR = 1.88). Furthermore, the hyper-responsiveness of the coronary vasculature to ET-1 induced by infusing the hearts with N(G)- monomethyl-L-arginine was markedly reduced by lercanidipine. These data clearly indicate that lercanidipine has potent anti-ischemic activity in low- flow perfused rabbit hearts and suggest that this activity is mostly confined to the (S)-enantiomer of the racemic lercanidipine. Moreover, the ability of lercanidipine to control the vasopressor activity of ET-1 further stresses the usefulness of this class of compounds for treatment of essential hypertension and vasospastic angina.

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