Influence of 3-cyano-2-morpholino-5-(päyrid-4-yl)pyridine (AWD 122-14) and dopamine on left ventricular function during acute volume load in 18-month-old spontaneously hypertensive rats and Wistar-Kyoto rats.
Effects of AWD 122-14, a new cardiotonic agent, and dopamine were studied in an experimental model of congestive heart failure in 12- and 18-month-old spontaneously hypertensive rats (SHR rats) in comparison to normotensive Wistar-Kyoto rats (WKY rats) as control group. This model combines an acute volume overloading with an already existing chronic pressure overload. Heart rate (HR), peak left ventricular pressure (PLVP), left ventricular enddiastolic pressure (LVEDP), and left ventricular contractility index (LV dp/dtmax) were significantly elevated in SHR rats versus WKY rats. Left ventricular mass (LVM) to body mass (bw) ratio was increased in SHR rats and there was a parallel, rightward shift of the left ventricular diastolic pressure-volume-relationship in the 18-month-old SHR rats. Thus for a given LVEDP, there is an increased left ventricular enddiastolic volume (LVEDV) in SHR rats, indicating a true structural outgrowth of the left ventricular lumen. During acute volume overloading LVEDP increased in the 12- and 18-month-old WKY rats and in the 12-month-old SHR rats. In contrast, the 18-month-old SHR rats showed no increase of the already very high baseline level of LVEDP. Dopamine and AWD 122-14 increased LV dp/dtmax in all groups. AWD 122-14 was able to reduce left ventricular filling pressure of the 18-month-old SHR rats. A further interesting finding was that AWD 122-14 reduced the content of thiobarbituric acid material in the left ventricle in the 18-month-old SHR rats (reduced lipid peroxidation), suggesting a possible cardioprotective action of this substance.
Rohde
E
E
Research Institut of Molecular Pharmacology, Berlin.
Wiesner
B
B
Blasig
I E
IE
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects*
D002316:Cardiotonic Agents; D009025:Morpholines; D011725:Pyridines; D017392:Thiobarbituric Acid Reactive Substances; C077469:3-cyano-2-morpholino-5-(pyrid-4-yl)pyridine; D004298:Dopamine