M. Shimabukuro et al., IMPAIRED MECHANICAL RESPONSE TO CALCIUM OF DIABETIC RAT HEARTS - REVERSAL BY NIFEDIPINE TREATMENT, Journal of cardiovascular pharmacology, 26(3), 1995, pp. 495-502
Streptozotocin-induced diabetic and age-matched control rats were trea
ted with 0.03% nifedipine-containing chow for 6 weeks, and mechanical
response to Ca2+ was studied using isolated working hearts. At 14 week
s of age, 7 weeks after a streptozotocin injection, diabetic rats had
a lower body weight and heart weight than controls, and an increase in
heart weight-to-body weight ratio. Nifedipine treatment did not alter
these parameters of controls, but decreased the heart weight and hear
t weight-to-body weight ratio of diabetic rats without affecting the b
ody weight. In diabetic rats, systolic blood pressure was decreased co
mpared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and redu
ced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In contr
ol rats, LV developed pressure, LV +/- dP/dt, and cardiac work were un
changed regardless of the increment in preload at 1.25, 1.88, and 2.50
mM Ca2+. However, the responses of diabetic rats were decreased with
an increment in preload at 2.5 mM Ca2+. Nifedipine treatment produced
a partial recovery of all four parameters at 2.5 mM Ca2+ in diabetic r
ats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation we
re similar in hearts from control and diabetic rats at all Ca2+ concen
trations and nifedipine treatment did not affect these values. Results
suggest that chronic nifedipine treatment improve the contractility o
f diabetic rat hearts under high Ca2+ conditions.