title: Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure.
abstract: Abnormalities in energy metabolism may play an important role in the development of hypertensive heart failure. However, the transition from compensated hypertrophy to heart failure is not fully understood in terms of energy metabolism. In Dahl salt-sensitive (DS) and salt-resistant (DR) rats, myocardial fatty acid and glucose uptake values were determined using (131)I- or (125)I-labeled 9-methylpentadecanoic acid ((131)I- or (125)I-9MPA), and [(14)C]deoxyglucose ([(14)C]DG), fatty acid beta-oxidation was identified using thin-layer chromatography, and insulin-stimulated glucose-uptake was observed using a euglycemic hyperinsulinemic glucose clamp. Six-week-old rats were fed a diet that contained 8% NaCl, which resulted in development of compensated hypertrophy in DS rats at 12 wk of age and ultimately led to heart failure by 18 wk of age. Uptake of [(14)C]DG increased markedly with age in the DS rats, whereas (131)I-9MPA uptake was marginally but significantly increased only in animals aged 12 wk. The ratio of (125)I-9MPA beta-oxidation metabolites to total uptake in the DS rats was significantly lower (P < 0.05) at 12 (37%) and 18 (34%) wk compared with at 6 (45%) wk. Insulin increased [(14)C]DG uptake more than twofold in the DS rats at 6 wk, although this increase was markedly attenuated at 12 and 18 wk (11 and 8%, respectively). Our data suggest that in a hypertrophied heart before heart failure, fatty acid oxidation is impaired and the capacity to increase glucose uptake during insulin stimulation is markedly reduced. These changes in both glucose and fatty acid metabolism that occur in association with myocardial hypertrophy may have a pathogenic role in the subsequent development of heart failure.
authors.affiliation: Second Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Fujii
authors.forename: Takashi
authors.initials: T
authors.lastname: Nozawa
authors.forename: Akihiko
authors.initials: A
authors.lastname: Igawa
authors.forename: Bun-ichi
authors.initials: B
authors.lastname: Kato
authors.forename: Norio
authors.initials: N
authors.lastname: Igarashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Nonomura
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Asanoi
authors.forename: Shusaku
authors.initials: S
authors.lastname: Tazawa
authors.forename: Minoru
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000818:Animals; D002303:Cardiac Output, Low / Q000209:etiology*; D002855:Chromatography, Thin Layer; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005227:Fatty Acids / Q000378:metabolism* / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006973:Hypertension / Q000150:complications* / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007462:Iodobenzenes / Q000493:pharmacokinetics; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D020303:Rats, Inbred Dahl
chemical_list: D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D007462:Iodobenzenes; C067799:4-iodophenyl-9-methylpentadecanoic acid; D003847:Deoxyglucose; D005947:Glucose