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Highly Protective Effects Of Chronic Oral Administration Of Nicorandil On The Heart Of Ageing Rats

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SUMMARY

1. We have tested the effects of 2 month oral treatment with the KATP opener, nitric oxide (NO) donor and anti-oxidant molecule nicorandil (0.1 mg/kg per day) on major physiological parameters and heart function of 4-, 12- and 24-month-old rats.

2. Several methods were used: (i) measurement of blood pressure using a non-invasive tail-cuff method; (ii) perfusion of isolated heart; (iii) lactate dehydrogenase (LDH) dosage; and (iv) measurement of monophasic action potential of rat isolated hearts.

3. Blood pressure and ventricular action potential duration regularly increase with age in control animals, whereas nicorandil restores these parameters in aged animals to levels present in young adult animals. Moreover, following ischaemia, nicorandil treatment improved isolated heart survival rate (100 vs 50% for nicorandil-treated rats and controls, respectively), heart work and left ventricular developed pressure, whereas it decreased cardiac cell damage (LDH release) and perfusion pressure.

4. This condition of chronic oral nicorandil treatment presents a strong potential in the improvement of cardiac function in normal and pathological ageing.
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Keywords: KATP channel; ageing; blood pressure; contractile function; heart function

Document Type: Research Article

Affiliations: 1: Groupe d’Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l’Endothelium, INSERM-CEA-Université Joseph Fourier, Grenoble and 2: Laboratoire Stress Cardiovasculaire et Pathologies Associées, Faculté de Pharmacie, Université Joseph Fourier, La Tronche, France

Publication date: May 1, 2002

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