Cardiovascular and metabolic changes in spontaneously hypertensive rats following streptozotocin administration.
OBJECTIVE
To investigate whether the high mortality rate that occurs in streptozotocin (STZ)-diabetic spontaneously hypertensive rats (SHR) is related to abnormalities in glycemic control, in hemodynamics and cardiac function, or in susceptibility to the occurrence of ventricular arrhythmias.


METHODS
Diabetes was induced in SHR and Wistar-Kyoto (WKY) rats by the intravenous injection of STZ 55 mg/kg. Intraperitoneal glucose tolerance tests were performed after six and 11 weeks. Blood pressure was measured in conscious rats at weeks 0 and 11 with a tail-cuff method and in anesthetized animals at week 12 through a cannulated artery. Response of myocardial function to rapid intravenous infusion of saline 10 mL/kg/min and the times of onset of ventricular arrhythmias during intravenous infusion of aconitine 20 micrograms/kg/min were determined in anesthetized rats at week 12. Plasma samples from the rats were assayed for glucose, insulin, triglycerides and carnitine.


RESULTS
STZ injection caused hyperglycemia, hypoinsulinemia and glucose intolerance equally in SHR and WKY. Diabetic SHR exhibited significant hypertriglyceridemia, depletion in plasma carnitine, impaired responses of blood pressure and myocardial function to rapid intravenous infusion of saline and a 37.5% mortality rate, whereas diabetic WKY did not exhibit these changes. SHR and WKY, diabetic or nondiabetic, were equally sensitive to the induction of ventricular arrhythmias by aconitine infusion.


CONCLUSIONS
Mortality of the STZ-diabetic SHR is not due to an exaggeration of the impaired glycemic control, but may be attributed to the occurrence of cardiac dysfunction. The development of life-threatening cardiac arrhythmias, while unlikely, cannot be completely excluded.
Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver.
S
S
Dai
S
S
Lee
M
M
Battell
J H
JH
McNeill
D000157:Aconitine / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D002331:Carnitine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced*; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy*; D007328:Insulin / Q000097:blood*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage; D013311:Streptozocin / Q000008:administration & dosage* / Q000009:adverse effects; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D012462:Saline Solution, Hypertonic; D014280:Triglycerides; D013311:Streptozocin; D002331:Carnitine; D000157:Aconitine