CONTRIBUTION OF SYSTEMIC BLOOD-PRESSURE TO MYOCARDIAL REMODELING IN UREMIC RATS

Left ventricular hypertrophy with diffuse inter-myocardiocytic fibrosis is a feature of uremia. The role of blood pressure and/or other cardiovascular uremic risk factors in cardiac remodeling is still uncertain. To determine the extent to which improvement of kidney function and the control of uremia-related risk factors are associated with a reduction of myocardial injury, we evaluated the effect of dietary protein restriction or the angiotensin-converting enzyme inhibitor lisinopril on cardiac structure in remnant kidney rats. One week after subtotal nephrectomy, Wistar rats were allocated to receive drinking water solution (group 1), 5 mg/kg per day lisinopril (group 2), or a low-protein diet (6%) (group 3) for 12 weeks. Groups 2 and 3 showed a comparable efficacy in preventing the expected rise in creatininemia, urinary protein excretion, and glomerulosclerosis. However, hypertension development was prevented only in group 2. Groups 1 and 3 developed a significant (P<.01) increase in left ventricular weight (2.45+/-0.1 and 2.5+/-0.5 mg/g body wt, respectively) compared with group 2 (1.9+/-0.06 mg/g body wt). Cardiac hydroxyproline concentration was also lower in group 2 compared with group 1 (2.07+/-0.16 versus 2.73+/-0.17 mg/g left ventricular weight, P<.05) but not compared with group 3 (2.59+/-0.19 mg/g left ventricular weight). The effect of angiotensin-converting enzyme inhibition on left ventricular mass and intracardiac collagen content appeared to be dissociated from anemia, sympathetic activity, and hyperlipidemia. There was a close relationship between systolic pressure and left ventricular mass; however, no relationship between the degree of cardiac fibrosis and systolic pressure could be determined. Compared with other uremia-related risk factors, control of systemic blood pressure is an essential component of the prevention of left ventricular hypertrophy, and the limitation of interstitial fibrosis may occur by a mechanism other than blood pressure control.