Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition.
This study examined the preventative effect of an aldose reductase inhibitor, ponalrestat, on contractile properties of heart left ventricular papillary muscles in rats having streptozotocin induced diabetes for 13 weeks. Both contraction and relaxation were slowed by diabetes. The time to reach peak twitch tension was increased by 21%, and the time to relax to half peak tension was increased by 29% (p less than 0.01, respectively compared to normal control animals). With ponalrestat treatment, the increase in contraction time was only 11%, and relaxation was only slowed by 4% (p less than 0.05 and p less than 0.01, respectively compared to diabetic controls). Diabetes also reduced maximum rates of contraction (13%) and relaxation (19%) and prolonged the time taken to reach peak relaxation rate (36%, p less than 0.01). Ponalrestat had no effect on maximum contraction rates but was particularly effective in normalising relaxation rates (p less than 0.01). Deficiencies with diabetes were noted over a range of stimulation frequencies (0.1-4.0 Hz), and ponalrestat treatment was beneficial except at the highest rates. Diabetes and ponalrestat effects were observed over a temperature range of 25-37 degrees C. Ventricular sorbitol levels showed a 17-fold increase with diabetes (p less than 0.01) and this was reduced by 67% with ponalrestat (p less than 0.01). There were no changes in ventricular myo-inositol. It is possible that ponalrestat treatment prevented a defect in sarcoplasmic reticulum calcium handling which could be responsible in part for the deficits in contraction ability and mainly for the deficits in relaxation ability in diabetic cardiomyopathy, although this remains to be tested directly.
Cameron
N E
NE
Department of Physiology, University of Aberdeen, Scotland, UK.
Cotter
M A
MA
Robertson
S
S
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013012:Sorbitol / Q000378:metabolism; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*; D013696:Temperature; D016276:Ventricular Function
D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase