OBJECTIVETo compare the effects of amlodipine, benidipine and nifedipine on myocardial hypertrophy and evaluate the underlying mechanism.

METHODSMyocardial hypertrophy model was created by transverse aortic constriction (TAC) in C57 BL/6 mice, and plasma catecholamine concentrations were measured 7 days after surgery to confirm the sympathetic activation. The 3 drugs were administered in TAC mice for 7 days and cardiac hypertrophy was evaluated according to the heart-to-body weight ratio (HW/BW). Effects of those drugs on the protein synthesis stimulated by phenylephrine in cultured neonatal cardiac myocytes were also examined.

RESULTSHW/BW and plasma concentrations of catecholamine were significantly increased in TAC mice one week after surgery in comparison with to sham-operated mice. One week after TAC, the HW/BW ratio was significantly lower in the amolodipine but not nifedipine-treated group than in the TAC group. Administration of nifedipine via minipump infusion for one week did not decrease HW/BW ratio. Treatment with amlodpine or benidipine, but not nifedipine, decreased the neonatal rat myocyte protein synthesis induced by phenylephrine stimulation.

CONCLUSIONAntihypertrophic effect of DHEs on myocardium is dependent on their potential of blocking N-type calcium channel, and the underlying mechanism involves the sympathetic inhibition.

Amlodipine ; pharmacology ; therapeutic use ; Animals ; Calcium Channel Blockers ; pharmacology ; therapeutic use ; Calcium Channels, N-Type ; drug effects ; Cardiomegaly ; drug therapy ; etiology ; Dihydropyridines ; pharmacology ; therapeutic use ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Nifedipine ; pharmacology ; therapeutic use

BACKGROUNDNitric oxide (NO) is a biologically active molecule which has been reported to protect the heart against ischemia and reperfusion injury in different species. This study aimed to test the hypothesis that nitric oxide may induce the expression of heat shock protein 72 (HSP72) which may protect the heart against ischemia.

METHODSRabbits were given intravenous saline or S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, or Zaprinast, an inhibitor of cyclic guanosine monophosphate (GMP)-phosphodiesterase, which may increase myocardial cyclic GMP content. Twenty-four hours later, the rabbits were either sampled to measure HSP72, or induced with a 30-minute coronary occlusion followed by a 120-minute reperfusion, and then the infarct size was measured. Meanwhile, chelerythrine (CHE, an inhibitor of protein kinase C) was given intravenously 5 minutes before SNAP injection and the effect on HSP72 expression and infarct size was determined.

RESULTSTwenty-four hours after pretreatment, immunoblotting showed HSP72 expression increased in the SNAP group compared with control groups, and this was blocked by CHE. Myocardial infarct size in the SNAP group was smaller than that of the control group ((32.4 +/- 5.8)% vs (51.1 +/- 4.7)%, P < 0.05). Pretreated with CHE abolished the infarct size-limiting effect of SNAP ((46.0 +/- 5.1)%). Pretreatment with Zaprinast neither induced HSP72 expression nor reduced infarct size ((55.4 +/- 5.4)%).

CONCLUSIONNO induced HSP72 expression and a delayed protection to the heart via the activities of protein kinase C by a cyclic GMP-independent pathway.

Animals ; Benzophenanthridines ; pharmacology ; Cyclic GMP ; metabolism ; HSP72 Heat-Shock Proteins ; biosynthesis ; Hemodynamics ; Male ; Myocardial Infarction ; metabolism ; physiopathology ; prevention & control ; Myocardial Ischemia ; metabolism ; physiopathology ; prevention & control ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; pharmacology ; Phosphodiesterase Inhibitors ; pharmacology ; Protein Kinase C ; metabolism ; Purinones ; pharmacology ; Rabbits ; S-Nitroso-N-Acetylpenicillamine ; pharmacology