P. Gohlke et al., CARDIAC AND VASCULAR EFFECTS OF LONG-TERM LOSARTAN TREATMENT IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS, Hypertension, 28(3), 1996, pp. 397-402
In previous studies in stroke-prone spontaneously hypertensive rats (S
HRSP), we demonstrated that early-onset, long-term angiotensin-convert
ing enzyme inhibitor treatment improved cardiac function and metabolis
m and increased aortic cGMP content even at sub-antihypertensive doses
. These effects could be prevented by bradykinin type 2 (B-2) receptor
blockade with icatibant. In the present study, we studied the effects
of long term oral treatment with the angiotensin type 1 (AT(1)) recep
tor antagonist losartan (30 mg/kg per day) on functional and biochemic
al parameters of the heart and on cGMP content in the aorta in SHRSP t
reated prenatally and subsequently up to the age of 20 weeks. Losartan
prevented the development of hypertension and left ventricular hypert
rophy. Cardiac function measured ex vivo in isolated perfused hearts w
as improved, as demonstrated by significant increases in left ventricu
lar pressure (22.4%), differentiated left ventricular pressure (dP/dt(
max)) (35.1%), and coronary flow (38%). The release of the intracellul
ar enzymes lactate dehydrogenase and creatine kinase and of lactate in
to the coronary effluent was reduced by 46.4%, 47.2%, and 63.6%, respe
ctively. In myocardial tissue, the concentrations of glycogen and the
energy-rich phosphates ATP and creatine phosphate were increased by 43
.2%, 33.1%, and 42.4%, respectively, whereas lactate was decreased by
57.0%. The aortic tissue content of cGMP was increased fivefold. Our r
esults demonstrate that chronic blockade of AT(1) receptors with losar
tan improved cardiac function and metabolism and increased aortic cGMP
content in SHRSP to an extent similar to that observed previously aft
er long-term angiotensin-converting enzyme inhibitor treatment at a co
mparably antihypertensive dose. Prevention of hypertension and cardiac
hypertrophy as well as stimulation of non-AT(1) receptors are discuss
ed to explain the cardiac and vascular actions of losartan.