Impaired mechanical response to calcium of diabetic rat hearts: reversal by nifedipine treatment.
Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca2+ was studied using isolated working hearts. At 14 weeks 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 heart weight-to-body weight ratio of diabetic rats without affecting the body weight. In diabetic rats, systolic blood pressure was decreased compared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and reduced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In control rats, LV developed pressure, LV +/- dP/dt, and cardiac work were unchanged 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 rats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca2+ concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca2+ conditions.
Shimabukuro
M
M
Second Department of Internal Medicine, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa.
Shinzato
T
T
Higa
S
S
Nagamine
F
F
Murakami
K
K
Takasu
N
N
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000378:metabolism / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D002118:Calcium; D006442:Glycated Hemoglobin; D007328:Insulin; D009543:Nifedipine