CONVERTING-ENZYME INHIBITION IMPROVES CONGESTION AND SURVIVAL IN HYPERTENSIVE RATS WITH HIGH-OUTPUT HEART-FAILURE

The effects of angiotensin-converting enzyme (ACE) inhibitors in high- output heart failure have not yet been well established. We evaluated the effects of lisinopril (3 mg/kg/day) on hemodynamics, neurohormones , and survival in 10-week-old spontaneously hypertensive rats (SHR) wi th aortocaval fistula. Sham-operated treated and untreated SHR served as controls. Cardiac output (CO) was determined by thermodilution meth od, and renal blood flow (RBF) was assessed by laser-Doppler flowmetry . In sham-operated SHR, 2-week treatment with lisinopril decreased blo od pressure (BP), left ventricular (LV) weight, and total peripheral r esistance (TPR) (p < 0.01 each) and increased RBF and plasma renin act ivity (PRA) (both p < 0.05); CO and LV end-diastolic pressure (LVEDP) were unchanged. Fistula creation induced biventricular hypertrophy and high-output heart failure [increased LVEDP, CO, pulse pressure, and p lasma norepinephrine (NE) and decreased RBF] with congestive signs (as cites, tachypnea). Lisinopril decreased LVEDP (p < 0.01), increased RB F, prolonged Survival (both p < 0.05), and prevented ascites (0 vs. 46 %) and increased PRA (p < 0.05) and attenuated the increase in plasma NE. Heart weight, BP, and CO were not affected by lisinopril. Thus, li sinopril ameliorated congestion and improved survival in SHR with fist ula without compromising cardiorenal hemodynamics. Venous and renal di latation and attenuation of vasoconstrictive systems may have contribu ted to the beneficial effects.