Document Detail


Influence of calcium channel blocker treatment on the mechanical properties of diabetic rat myocardium.
MedLine Citation:
PMID:  8777289     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The objective of this investigation was to determine whether calcium channel blocker (CCB) treatment effectively restores normal baseline mechanical function in diabetic myocardium and to evaluate its effect on the interval-strength relationship. Wistar rats were made diabetic with streptozotocin (55 mg/kg, IV). Left-ventricular papillary muscles from normal and diabetic (10 weeks) rats were superfused with Tyrode's solution at 30 degrees C. A subgroup of diabetic and normal animals received daily injections of verapamil or nifedipine (10 mg/kg, IP; 8 weeks) to compare the effectiveness of a phenylalkylamine to a dihydropyridine in reversing diabetes-induced contractile dysfunction in vitro. Muscles were electrically stimulated at 0.5 Hz with suprathreshold stimuli, and the following parameters were measured: peak tension developed, time to-peak tension, time-to-90% relaxation, and the maximum velocities of tension development and decay. Experimental diabetes was characterized by: severe hyperglycemia, hepatomegaly, reduced body weight gain, cardiomegaly, and increased plasma phospholipid levels. In addition, baseline values of peak tension developed, time to-peak tension, and time-to-90% relaxation were significantly greater in muscles from diabetic animals. Chronic nifedipine treatment reduced hyperglycemia and plasma phospholipid levels, normalized body weight gain, and reduced both heart and liver sizes in diabetic animals. Nifedipine treatment completely reversed diabetes-induced prolongation in both time-to-peak tension and time-to-90% relaxation. In diabetic myocardium, a slightly positive component was present in the interval-strength relationship between 0.01 and 1 Hz, resulting in a rightward shift in the entire curve across a wide range of stimulation frequencies (0.01-5 Hz). This positive component was absent in muscles from diabetic animals treated with both CCBs, and verapamil produced a leftward shift in the frequency response curve. The results of this study suggest that chronic nifedipine treatment may be more effective than verapamil in restoring normal baseline myocardial mechanical function, reducing hyperglycemia and hyperlipidemia, as well as attenuating both cardiac and liver enlargement in experimental diabetes. In contrast, verapamil treatment tended to normalize more effectively the inotropic response to changes in stimulation frequency in diabetic myocardium.
Authors:
R A Brown; M M Lee; A M Sundareson; D J Woodbury; A O Savage
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Acta diabetologica     Volume:  33     ISSN:  0940-5429     ISO Abbreviation:  Acta Diabetol     Publication Date:  1996 Mar 
Date Detail:
Created Date:  1996-09-16     Completed Date:  1996-09-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9200299     Medline TA:  Acta Diabetol     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  7-14     Citation Subset:  IM    
Affiliation:
Department of Physiology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Blood Glucose / metabolism
Body Weight
Calcium Channel Blockers / pharmacology*
Diabetes Mellitus, Experimental / blood,  physiopathology*
Heart / drug effects*,  physiology,  physiopathology
Lactates / blood
Liver / drug effects
Male
Myocardial Contraction / drug effects*
Nifedipine / pharmacology*
Organ Size
Papillary Muscles / drug effects*,  physiology,  physiopathology
Phospholipids / blood
Rats
Rats, Wistar
Reference Values
Verapamil / pharmacology*
Grant Support
ID/Acronym/Agency:
GM08167/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Calcium Channel Blockers; 0/Lactates; 0/Phospholipids; 21829-25-4/Nifedipine; 52-53-9/Verapamil

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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