Comparison of the effects of ACE inhibition with those of angiotensin II receptor antagonism on systolic and diastolic myocardial stunning in isolated rabbit heart.
The aim was to determine whether enalaprilat (0.08 mg/kg/min) or losartan (0.01 mg/kg/min) administration before ischemia can improve postischemic systolic and diastolic dysfunction ('stunned myocardium') and attenuate the 'hyperfunction' phase at the beginning of reperfusion. An isolated isovolumic rabbit heart preparation was subjected to 15 min of ischemia followed by 30 min of reperfusion without (group 1) or with pretreatment with enalaprilat (group 2) or losartan (group 3). Left ventricular developed pressure and end-diastolic pressure (diastolic stiffness) were measured and the time constant of isovolumic relaxation (T, Tau) and the ratio between +dP/dt and -dP/dt were calculated. In comparison to the stunned group (group 1) both enalaprilat (group 2) and losartan (group 3) exerted a significant protective effect on postischemic recovery of contractile state and diastolic stiffness. Only enalaprilat attenuated the 'hypercontractile' phase. However, both enalaprilat and losartan failed to improve myocardial relaxation. In summary, these data strongly suggest a direct deleterious action of the local renin-angiotensin system on ischemic myocardium and diminution of myocardial stunning with its successful blockade. Although, we can not exclude the possibility that bradykinin has some cardioprotective effect, these data suggest that angiotensin exacerbates myocardial injury.
Departamento de Patología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
C
C
Morales
M
M
Rodríguez
O
O
Scapín
R J
RJ
Gelpi
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D003971:Diastole; D015773:Enalaprilat / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D017682:Myocardial Stunning / Q000503:physiopathology / Q000517:prevention & control*; D011817:Rabbits; D013599:Systole
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D015773:Enalaprilat; D019808:Losartan