Contractile responses to various inotropic agents in isolated hearts obtained from hypertensive diabetic rats.
The profile of the contractile effects of calcium ions, the Ca(2+)-entry promoter Bay K 8644 and two alpha 1-adrenoceptor agonists (cirazoline and ST587) was studied in isolated perfused Langendorff hearts taken from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) with simultaneous diabetes. In both the hypertensive and the diabetic state the isolated hearts showed a tendency to an impaired inotropic response (increase in left ventricular pressure (LVP)) towards an increase of extracellular calcium ions. The impaired inotropic response was most pronounced in hearts of rats with simultaneous diabetes and hypertension. The Ca(2+)-influx promoter Bay K 8644 did not influence the maximally developed LVP in (diabetic) SHR and WKY preparations. The inotropic responses to both cirazoline and ST587 were increased in hearts from diabetic WKY and diabetic SHR, when compared with those from control WKY and SHR. Hypertension, however, blunted the inotropic response to ST587 but not that to cirazoline when compared to hearts from control WKY or diabetic WKY. The present study indicates that the combination of hypertension and diabetes leads to progressive cardiac deterioration, likely to be the result of important changes in calcium homeostasis.
Beenen
O H
OH
Department of Pharmacotherapy, University of Amsterdam, Academic Medical Centre, The Netherlands.
Pfaffendorf
M
M
van Zwieten
P A
PA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000627:therapeutic use; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D004353:Drug Evaluation, Preclinical; D006706:Homeostasis / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D007093:Imidazoles / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000316:Adrenergic alpha-Agonists; D002120:Calcium Channel Agonists; D002316:Cardiotonic Agents; D007093:Imidazoles; C030655:St 587; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D003000:Clonidine; C014282:cirazoline; D002118:Calcium