Alcohol-induced reductions in cardiac protein synthesis in vivo are not ameliorated by treatment with the dihydropyridine calcium channel blocker amlodipine.
BACKGROUND
Various studies have indicated that acute ethanol dosage perturbs cardiac function and/or structure with concomitant reductions in protein synthesis. Cellular calcium homeostasis is also perturbed, which may contribute to altered protein synthesis. This is supported by the observation that calcium channel blockers can prevent numerous features of alcohol-induced pathology. However, many of these studies have been carried out in vitro, employing supraphysiological levels of alcohol, or have failed to address whether their results obtained in isolated systems have direct relevance in vivo. The aim of the present investigation was to examine the response of cardiac protein synthesis in vivo due to a physiologically relevant dose of ethanol and determine whether a calcium channel antagonist could prevent these effects.


METHODS
Changes in cardiac protein synthesis rates in vivo were assessed by measuring the fractional rates of protein synthesis (i.e., ks) using a "flooding dose" of [3H]phenylalanine. Rats were treated either acutely (10 mg/kg body weight, 3 hr) or chronically (10 mg/kg body weight/day, 30 days) with amlodipine, a dihydropyridine-type calcium channel blocker, before dosing with ethanol (75 mmol/kg body weight, 2.5 hr).


RESULTS
Ethanol (75 mmol/kg body weight) inhibited cardiac protein synthesis after 1 hr. Similar responses were recorded at 2.5 and 6 hr after ethanol dosage. At 24 hr, ethanol decreased food intakes. However, a direct comparison between pair-fed controls and alcohol-dosed rats also showed a decrease in cardiac protein synthesis after 24 hr. Acute alcohol dosage reduced cardiac protein synthesis in mixed, myofibrillary, and sarcoplasmic protein fractions. Similar results were obtained when data were expressed relative to ribonucleic acid (i.e., kRNA). Neither acute nor chronic treatments with the calcium antagonist amlodipine ameliorated the deleterious actions of ethanol on protein synthesis.


CONCLUSIONS
Ethanol may affect cardiac protein synthesis independently of altered calcium entry.
Patel
V B
VB
Department of Clinical Biochemistry, Guy's, King's and St. Thomas' Medical School, King's College London, UK.
Siddiq
T
T
Richardson
P J
PJ
Preedy
V R
VR
D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D010649:Phenylalanine / Q000096:biosynthesis / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D002492:Central Nervous System Depressants; D009124:Muscle Proteins; D011500:Protein Synthesis Inhibitors; D017311:Amlodipine; D000431:Ethanol; D010649:Phenylalanine