Characterization of contractile function in diabetic hypertensive cardiomyopathy in adult rat ventricular myocytes

Diabetes and hypertension both produce myocardial dysfunction that accelera tes cardiovascular morbidity and mortality. Coexistence of the two often re sults in a more severe cardiomyopathy than either process alone. The purpos e of this Study was to characterize the contractile function of diabetic hy pertensive cardiomyopathy at the single myocyte level. Adult spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were made diabetic with a single injection (55 mg/kg) of streptozotocin (STZ). Contra ctile properties of ventricular myocytes were evaluated, including peak sho rtening (PS). time-to-peak shortening (TPS), time-to-90%, relengthening (TR 90) and maximal velocities of shortening/relengthening (dL/dt). The experim ental animals exhibited enlarged heart size. elevated blood glucose and sys tolic blood pressure. PS was unchanged (SHR), enhanced (WKY-STZ) or depress ed (SHR-STZ) compared to control (WKY). Myocytes from all experimental grou ps displayed prolonged TPS and TR,,, compared to the WKY group. although on ly those from the hypertensive groups (SHR. SHR-STZ) were associated with r educed +/- dL/dt. Additionally, myocytes from the WKY-STZ but not the SHR o r the SHR-STZ groups exhibited impaired responsiveness to increased extrace llular Ca2+. Myocytes from the SHR-STZ group displayed a leftward shift of the stimulus frequency-peak shortening response curve compared to the WKY g roup. These results confirmed observations at the multicellular levels that combination of diabetes and hypertension results in a greater impairment o f cardiac contractile function than is seen with either disease alone. (C) 2001 Academic Press.