Highly protective effects of chronic oral administration of nicorandil on the heart of ageing rats.
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.
Garnier-Raveaud
Stéphanie
S
Groupe d'Electrophysiologie Moléculaire, Laboratoire de Développement et Vieillissement de l'Endothelium, INSERM-CEA-Université Joseph Fourier, Grenoble, France.
Faury
Gilles
G
Mazenot
Catherine
C
Cand
Francine
F
Godin-Ribuot
Diane
D
Verdetti
Jean
J
D000284:Administration, Oral; D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017202:Myocardial Ischemia / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology; D020108:Nicorandil / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D016277:Ventricular Function, Left / Q000187:drug effects
D000975:Antioxidants; D020030:Nitric Oxide Donors; D015221:Potassium Channels; D020108:Nicorandil; D007770:L-Lactate Dehydrogenase