Effect of angiotensin type I-receptor blockade on left ventricular remodeling in pressure overload hypertrophy.
BACKGROUND
The renin-angiotensin system is involved in cardiac remodeling. In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (AT(1))-receptor blockade on left ventricular (LV) hypertrophy and dysfunction is controversial.


RESULTS
Descending thoracic aorta-banded and sham-operated guinea pigs were given either losartan (30 mg x kg(-1) x day(-1) intraperitoneally) or vehicle for 8 weeks (n = 7 in each group). LV end-diastolic and end-systolic dimensions and wall thicknesses were measured echocardiographically, and LV fractional shortening, relative wall thickness, and LV mass normalized by body weight were calculated. Isolated heart function (Langendorff perfusion) was studied 8 weeks after surgery, and LV performance was assessed by maximum LV pressure and +/-dP/dt normalized by LV mass. Eight weeks after banding guinea pigs developed concentric LV hypertrophy and had decreased maximum LV pressure and +/-dP/dt normalized by LV mass; LV end-diastolic dimension and LV fractional shortening were unchanged. In band-operated guinea pigs treatment with losartan had no significant effects on any of these measurements.


CONCLUSIONS
In guinea pigs with descending aortic banding, treatment with losartan for 8 weeks neither attenuates progression of pressure overload hypertrophy nor significantly improves impaired mass-normalized pressure-derived indices of LV contraction and relaxation.
Kiatchoosakun
S
S
Department of Medicine, University Hospitals of Cleveland and Case Western Reserve University, Cleveland, OH 44106-5038, USA.
Lawrence
E
E
Nakada
S
S
Restivo
J
J
Walsh
R A
RA
Hoit
B D
BD
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004452:Echocardiography; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D019808:Losartan / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008955:Models, Cardiovascular; D009929:Organ Size / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000627:therapeutic use*; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019808:Losartan