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) with aortocaval fistula. Sham-operated treated and untreated SHR served as controls. Cardiac output (CO) was determined by thermodilution method, and renal blood flow (RBF) was assessed by laser-Doppler flowmetry. In sham-operated SHR, 2-week treatment with lisinopril decreased blood pressure (BP), left ventricular (LV) weight, and total peripheral resistance (TPR) (p < 0.01 each) and increased RBF and plasma renin activity (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 plasma norepinephrine (NE) and decreased RBF] with congestive signs (ascites, tachypnea). Lisinopril decreased LVEDP (p < 0.01), increased RBF, 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, lisinopril ameliorated congestion and improved survival in SHR with fistula without compromising cardiorenal hemodynamics. Venous and renal dilatation and attenuation of vasoconstrictive systems may have contributed to the beneficial effects.
Nishimura
H
H
Third Department of Internal Medicine, Osaka Medical College, Japan.
Oka
T
T
Ueyama
M
M
Kubota
J
J
Kawamura
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D017706:Lisinopril