Effect of sulfo-N-succinimidyl palmitate on the rat heart: myocardial long-chain fatty acid uptake and cardiac hypertrophy.
Abnormal long-chain fatty acid metabolism has been suggested as having a role in the genesis of certain cardiac diseases, and depressed myocardial long-chain fatty acid uptake has been clinically demonstrated in some patients with hypertrophic cardiomyopathy. However, the site where long-chain fatty acid metabolism is affected in cardiomyopathy remains unclear. Although cardiac hypertrophy is reported to be induced in rats by a fat-free diet, little is known of the consequences of depressed myocardial long-chain fatty acid uptake. Sulfo-N-succinimidyl derivatives of long-chain fatty acids have been shown to irreversibly inhibit long-chain fatty acid transport. To investigate the possible linkage of abnormal long-chain fatty acid uptake with cardiac hypertrophy, myocardial long-chain fatty acid uptake was blocked in rats using a sulfo-N-succinimidyl derivative of palmitate (SSP). SSP was intraperitoneally administered to rats for 12 weeks, and its effects on physiological parameters, and cardiac morphology were studied, SSP treatment (20 mg/kg) caused a 12% increase in heart weight (663.7 +/- 33.6 mg in controls v 741.2 +/- 26.5 mg after SSP treatment) and an 11% increase in the heart weight to body weight ratio (2.46 +/- 0.10 in controls v 2.72 +/- 0.17 after SSP) without any significant change of body weight. No significant differences were observed in blood pressure, heart rate, and serum hormones (insulin and triiodothyronine) between the control and SSP-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Kusaka
Y
Y
Department of Internal Medicine, Osaka Medical College, Japan.
Tanaka
T
T
Okamoto
F
F
Terasaki
F
F
Matsunaga
Y
Y
Miyazaki
H
H
Kawamura
K
K
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007328:Insulin / Q000097:blood; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010168:Palmitates / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013388:Succinimides / Q000494:pharmacology*; D013462:Sulfur Radioisotopes; D013599:Systole / Q000187:drug effects; D014018:Tissue Distribution; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D001798:Blood Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates; D013388:Succinimides; D013462:Sulfur Radioisotopes; D014280:Triglycerides; C097197:sulfo-N-succinimidyl palmitate; D014284:Triiodothyronine; D002784:Cholesterol