Effects of tedisamil on cardiovascular tissues isolated from normo- and hypertensive rats.
BACKGROUND
This study was undertaken to characterize the effects of tedisamil on isolated rat cardiovascular tissues, and identify actions that could be beneficial or detrimental in the treatment of cardiac disease.


RESULTS
Tedisamil prolonged the Wistar Kyoto normotensive rat (WKY) left ventricular action potential and augmented the force of contraction of left ventricle strips. On the 12-month-old SHR model of cardiac hypertrophy, the augmenting effects of tedisamil at 10(-6) and 3 x 10(-6) M were reduced. On the 21-month-old SHR model of heart failure, the augmenting effects of tedisamil at 10(-6) and 3 x 10(-6) M were further reduced. The augmenting effect of tedisamil at 10(-5) M was reduced to 47%. The rate of the right atrium of 16- to 17-month-old WKY was reduced by tedisamil at 10(-5) and 10(-4) M, and tedisamil had a similar effect on the SHR right atrium. Tedisamil at 10(-6)--3 x 10(-5) M contracted the portal veins of WKY and aortae of 12-month-old WKY and SHR.


CONCLUSIONS
The positive inotropic and negative chronotropic effects of tedisamil in the rat, which are partially or fully maintained in hypertrophied or failing myocardium would be beneficial in the treatment of heart failure. In contrast, the vasoconstrictor action of tedisamil will be detrimental in heart failure.
Doggrell
S A
SA
Cardiovascular Pharmacology Group, Faculty of Medicine and Health Sciences, The University of Auckland, New Zealand.
Nand
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D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D006332:Cardiomegaly / Q000188:drug therapy; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003521:Cyclopropanes / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006973:Hypertension / Q000188:drug therapy; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002316:Cardiotonic Agents; D003521:Cyclopropanes; C059921:tedisamil