THE EFFECT OF AT(1) RECEPTOR ANTAGONIST ON CHRONIC CARDIAC RESPONSE TO CORONARY-ARTERY LIGATION IN RATS

Objective: The aim was to study the effect of the AT, receptor antagon ist losartan on hemodynamic and morphometric changes following experim ental infarction. Methods: Experimental infarction was produced in adu lt male rats by ligating the coronary artery. Treatment with losartan was compared to untreated controls, in rats with experimental infarcti on and sham-operated animals. Results: Infarcted hearts were character ized by significant decreases in left ventricular developed pressure, as well as positive and negative (dP/dt)(max), whereas left ventricula r end-diastolic pressure (LVEDP), relaxation constant tau and right ve ntricular systolic pressure (RVSP) significantly increased. Treatment with losartan decreased the LVEDP, the relaxation constant tau and RVS P in the infarcted hearts. Right ventricular weight significantly incr eased in rats with infarction; this was attenuated by losartan. Infarc t size was not significantly influenced by losartan treatment. Morphom etric data revealed decreased capillary supply in infarcted hearts, es pecially in regions close to infarction; the decrease was less pronoun ced after losartan treatment. Capillary density in near infarct region decreased from 2826/mm(2) to 1471/mm(2) in untreated animals but in t he treated animals it decreased from 2982/mm(2) to only 2037/mm(2) Sim ultaneous significant decrease in myocyte-to-capillary ratio in treate d animals compared to untreated rats (0.87 to 0.67) seems to indicate formation of new capillary channels after losartan treatment. LVEDP wa s dependent on the size of infarction in untreated but not in treated animals. A close correlation between LVEDP and capillary density was f ound. Conclusions: Decreased ventricular contractility, prolonged rela xation and decreased coronary capillary density in rat experimental ca rdiac infarction confirm and amplify previous reports dealing with thi s experimental model. Moreover, we have found evidence of improved hem odynamics and coronary angiogenesis after losartan treatment.