Attenuation of left ventricular dysfunction by an ACE inhibitor after myocardial infarction in a kininogen-deficient rat model.
Bradykinin (BK) coronary outflow and left ventricular (LV) performance of kininogen-deficient Brown Norway Katholiek (BNK) rats and Brown Norway Hannover (BNH) controls were investigated. We analyzed whether the angiotensin-converting enzyme (ACE) inhibitor ramipril is able to attenuate LV dysfunction after induction of myocardial infarction (MI) in this animal model. Ex vivo, the basal BK content in the coronary outflow of buffer-perfused, isolated hearts was measured by specific radioimmunoassay. In vivo, left ventricular pressure (LVP), the maximal rate of LVP increase, LV end-diastolic pressure, the maximal rate of LVP decrease and heart rate were determined using a tip catheter 3 weeks after induction of MI. Compared to BNK rats, basal BK outflow was increased 30-fold in controls (p<0.01). In vivo, we found no significant differences between sham-ligated BNK and BNH rats in basal LV function. After MI, the impairment of LV function was significantly worse in BNK rats when compared to BNH rats. ACE inhibition significantly attenuated this LV dysfunction in both groups, when compared to untreated animals. Reduced basal BK level resulting from kininogen deficiency has no effect on basal LV function, but remains to be a risk factor for the ischemic heart. However, ACE inhibition is sufficient to improve LV function despite kininogen deficiency.
Koch
Matthias
M
Department of Cardiology and Pneumology, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, D-12200 Berlin, Germany.
Bonaventura
Klaus
K
Spillmann
Frank
F
Dendorfer
Andreas
A
Schultheiss
Heinz-Peter
HP
Tschöpe
Carsten
C
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001920:Bradykinin / Q000378:metabolism; D007704:Kininogens / Q000172:deficiency* / Q000235:genetics; D008297:Male; D009154:Mutation; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism*; D017257:Ramipril / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007704:Kininogens; D017257:Ramipril; D001920:Bradykinin