Myocardial and metabolic abnormalities in streptozotocin-diabetic Wistar and Wistar-Kyoto rats.
Four-week-old Wistar and Wistar-Kyoto (WKY) and 12-year-old Wistar rats treated with streptozotocin (55 or 65 mg/kg) were studied to assess the relationship between diabetes-induced alterations in lipid and thyroid hormone concentrations and myocardial tissue function. In the Wistar rats, both doses of streptozotocin resulted in hyperlipidemia and hypothyroidism. However, the higher dose was associated with: greater increases in plasma lipid levels in both age groups; larger increases in plasma lipid levels in older rats; and decreases in myocardial sensitivity to isoproterenol and beta-adrenoceptor density. The diabetic state in WKY rats, while also accompanied by hypothyroidism, was not differentially affected by the two doses of streptozotocin, nor associated with severe hyperlipidemia, nor associated with alterations in the myocardial beta-adrenoceptor system. These findings, as expected, reveal that the dose of streptozotocin and the age and strain of rat influence the diabetic state. Furthermore, these data do not suggest a direct correlation between diabetes-induced alterations in myocardial inotropic sensitivity and associated changes in plasma lipid or thyroid hormone concentrations.
Ramanadham
S
S
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver.
Doroudian
A
A
McNeill
J H
JH
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006949:Hyperlipidemias / Q000139:chemically induced*; D007037:Hypothyroidism / Q000139:chemically induced*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013311:Streptozocin / Q000008:administration & dosage
D011943:Receptors, Adrenergic, beta; D013311:Streptozocin; D007545:Isoproterenol; D002118:Calcium