Impaired cell communication in the diabetic heart. The role of the renin angiotensin system.
The influence of diabetes mellitus on the process of cell communication and impulse propagation was investigated in trabeculae isolated from the ventricle of diabetic rat hearts. Diabetes was produced by a single intraperitoneal injection of streptozotocin (60 mg/Kg). Cell-to-cell spread of Lucifer yellow CH was studied with the cut-end method. Measurements of the diffusion coefficient of Lucifer Yellow CH (D) was made by fitting the experimental results to theoretical points using an interactive computer program for non-linear regression. The results indicated an average value of D of 3 +/- 0.8x10(-7 )cm(2)/s for the controls (n = 5) and 3.8 +/- 0.5x10(-8 )cm(2)/s (n = 7) (p < 0.05) for diabetic hearts. No change of efflux of the dye through the surface cell membrane was found in diabetic rat compared to controls (p > 0.05). Moreover, the dye binding in the cytosol of diabetic heart was not significantly different from controls. The calculated values of junctional permeability for the dye was found to be p (j) = 1.5x10(-3 )cm/s for control and 1.5x10(-5 )cm/s for diabetic heart. To investigate the possible role of the activation of the renin-angiotensin system (RAS) on the change in cell communication, diabetic rats were treated with enalapril (25 mg/Kg/day) for a period of 14 days. Measurements of the diffusion coefficient (D) of the dye indicated a significant increase of D (6.7 +/- 1.1x10(-7 )cm(2)/s) (n = 4) (p < 0.05) compared with diabetic rats not exposed to enalapril. No change on efflux of the dye or cytoplasmic binding was found in animals treated with enalapril. The calculated value of junctional permeability showed a significant increase (p (j) = 3.9x10(-4 )cm/s) in presence of enalapril compared with controls. In addition, angiotensin II (10(-8 )M) added to the bath caused a significant decrease of conduction velocity in cardiac muscle of diabetic heart. In conclusion, Cell communication and impulse propagation are significantly impaired in the ventricle from diabetic rats, a phenomenon partly related to the activation of the RAS.
De Mello
Walmor C
WC
Department of Pharmacology, School of Medicine, Medical Sciences Campus, UPR, PO Box 365067, San Juan, PR 00936-5067, USA. wmello@rcm.upr.edu
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004058:Diffusion; D004656:Enalapril / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000378:metabolism; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology*; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*
D000959:Antihypertensive Agents; D005456:Fluorescent Dyes; D007546:Isoquinolines; D004656:Enalapril; C017475:lucifer yellow