Progression and regression of ventricular hypertrophy induced by left ventricular pressure overload.

The progression and regression of left ventricular hypertrophy (LVH) was studied in rats with pressure overload. Twelve adult male Sprague-Dawley rats were subjected to suprarenal descending aortic banding with tantalum clips. Three rats had sham operations (sham). After 10 weeks, three of the banded rats underwent left ventricular pressure measurements and were killed while the others had the clips removed. For 15 weeks after clip removal, separate groups of 3 rats were treated with losartan, captopril, and no medical therapy. The sham rats were not treated. Serial transthoracic echocardiography was performed on the sham rats and 6 of the banded rats before and after clip removal. After 15 weeks, all remaining rats underwent left ventricular pressure measurements, were killed and the hearts were removed for evaluation of left ventricular mass (LVM), beta-adrenergic receptor density (β-AR), angiotensin II receptor density (AII-R), and hydroxyproline content (OH-P). Plasma renin activity (PRA) was also measured. During aortic banding, systolic diameter (SD) tended to increase and fractional shortening (FS) tended to decrease, while diastolic diameter did not appear to change. After clip removal, SD decreased, and the FS increased toward those of the sham rats. None of the echocardiographic variables reached statistical significance. LVM indexed by total body mass (LVMI) was higher in the rats killed after 10 weeks of aortic banding compared to the sham rats (p=0.03). Five weeks after clip removal, LVMI was lower compared to the rats killed after 10 weeks of aortic banding; P=0.08: no medication, P=0.04: losartan, P=0.02: captopril. LVMI was lower in the captopril treated rats compared with the losartan treated rats (p=.04). There was no significant difference in the left ventricular pressures of the rats treated with losartan, captopril, or no medicine. There were also no statistically significant differences in the amount of OH-P in the left ventricular tissue. PRA was significantly elevated only in the captopril treated rats. The total β-AR was markedly higher in the group of rats killed after 10 weeks of aortic banding compared to the sham rats (p=0.0007), and appeared to decrease back toward a normal level in the rats with the clips removed. The β-AR was also significantly correlated with the LVMI (r=0.60, P=0.02). The AII-R was elevated in the hearts of the rats killed after 10 weeks of aortic banding but, unlike the β-AR, medical therapy appeared to increase the rate at which the levels returned toward normal. The AII-R was also significantly correlated with the LVMI (r=0.65, P=0.007). These data demonstrate that in rats after 10 weeks of aortic banding, LVH develops with mild systolic dysfunction but no overt dilation. LVH decreases after pressure overload is removed by unclipping and addition of captopril to the unclipped rats totally reversed LVH. Systolic function also appeared to improve after pressure overload ceased, but the effect of medications was indistinct. β-AR and AII-R increased with LVH and improved as the LVH resolved.