Positive inotropic responses of the sodium channel modulator BDF 9148 in diseased rat myocardium.
1. This study has defined the positive inotropic responses to the sodium channel modulator BDF 9148 in rats with hypertension, thyroid dysfunction, diabetes or dwarfism. Concentration-response curves to BDF 9148 and calcium chloride were determined in isolated left atria and left ventricular papillary muscles. 2. BDF 9148 increased force of contraction in left ventricular papillary muscles in all disease states with maximal responses comparable to calcium chloride. BDF 9148 potency was significantly decreased in muscles from diabetic rats only. 3. BDF 9148 produced similar responses in left atria except from hyperthyroid rats where negative inotropic responses only were measured. This exception confirms that the left atria is an imperfect model for ventricular responsiveness. 4. Thus, the increase in force of contraction in the ventricles as a consequence of sodium channel modulation by BDF 9148 is maintained in these disease states unlike responses to alpha-or beta-adrenoceptor agonists.
Hoey
A
A
Department of Physiology and Pharmacology, University of Queensland, Brisbane, Australia.
Nankervis
R
R
Brown
L
L
D000818:Animals; D001384:Azetidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002122:Calcium Chloride / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004392:Dwarfism / Q000188:drug therapy / Q000503:physiopathology; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology; D006980:Hyperthyroidism / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects
D001384:Azetidines; D002316:Cardiotonic Agents; D015222:Sodium Channels; C071117:BDF 9148; D002122:Calcium Chloride