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 pertur bs cardiac function and/or structure with concomitant reductions in protein synthesis. Cellular calcium homeostasis is also perturbed, which may contr ibute to altered protein synthesis. This is supported by the observation th at calcium channel blockers can prevent numerous features of alcohol-induce d 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 t hese effects. Methods: Changes in cardiac protein synthesis rates in vivo were assessed b y measuring the fractional rates of protein synthesis (i.e., k(s)) using a "flooding dose" of [H-3]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 d osing with ethanol (75 mmol/kg body weight, 2.5 hr). Results: Ethanol (75 mmol/kg body weight) inhibited cardiac protein synthes is after 1 hr. Similar responses were recorded at 2.5 and 6 hr after ethano l dosage. At 24 hr, ethanol decreased food intakes. However, a direct compa rison between pair-fed controls and alcohol-dosed rats also showed a decrea se in cardiac protein synthesis after 24 hr. Acute alcohol dosage reduced c ardiac protein synthesis in mixed, myofibrillary, and sarcoplasmic protein fractions. Similar results were obtained when data were expressed relative to ribonucleic acid (i.e., k(RNA)). Neither acute nor chronic treatments wi th 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.