Effects of various calcium antagonists in isolated perfused hearts from diabetic and age-matched control rats.
The purpose of this study was to examine the effects of several calcium antagonistic drugs on left ventricular contraction (isovolumetric) and coronary flow in isolated perfused hearts from streptozotocin diabetic rats compared to age-matched controls, thereby hoping to throw further light on the changes in Ca2+ handling that occur in the diabetic heart. In the presence of Ca2+ (0.9-9.9 mM) left ventricular pressure (LVP) was not significantly different in either type of heart. From cumulative dose-response curves, pD2 values of various calcium antagonists for the negative inotropic activity were determined in diabetic and control hearts. The pD2 values for several calcium antagonists were significantly greater in diabetic hearts than in controls: 5.72 vs. 4.99 for diltiazem, 6.88 vs. 6.60 for verapamil, and 8.42 vs. 8.04 for (-)-devapamil. In hearts from diabetic rats, LVP was also more sensitive to TMB-8 compared with controls: a higher pEC20 value (instead of the pD2 value) was found (5.47 vs. 5.16). The pD2 values for (+)-devapamil, nifedipine, and ryanodine were not significantly different in either type of heart. Calcium-entry blockers increased the coronary flow in control hearts (range 60-80% of the initial flow). However, the increase in flow was significantly greater in diabetic hearts than in the controls (95-128%). TMB-8 and ryanodine had no effect on coronary flow in both types of hearts. In conclusion, the changes in sensitivity of LVP to several calcium antagonists may support a different Ca2+ handling in diabetic hearts compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Heijnis
J B
JB
Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
Mathy
M J
MJ
van Zwieten
P A
PA
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003864:Depression, Chemical; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000633:toxicity; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D002118:Calcium