T. Sladek et al., THE EFFECT OF AT(1) RECEPTOR ANTAGONIST ON CHRONIC CARDIAC RESPONSE TO CORONARY-ARTERY LIGATION IN RATS, Cardiovascular Research, 31(4), 1996, pp. 568-576
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.