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Converting enzyme inhibition improves congestion and survival in hypertensive rats with high-output heart failure
1Third Department of Internal Medicine, Osaka Medical College, Japan.
Insights
Lisinopril improved survival and reduced congestion in rats with high-output heart failure. This angiotensin-converting enzyme inhibitor treatment did not negatively impact cardiorenal hemodynamics.
Area of Science:
- Cardiology
- Pharmacology
- Renal Physiology
Background:
- High-output heart failure (HOHF) effects are not well understood.
- Angiotensin-converting enzyme (ACE) inhibitors' role in HOHF requires further investigation.
Purpose of the Study:
- To evaluate lisinopril's effects on hemodynamics, neurohormones, and survival in a rat model of HOHF.
- To assess lisinopril's impact on spontaneously hypertensive rats (SHR) with an aortocaval fistula.
Main Methods:
- Utilized spontaneously hypertensive rats (SHR) with surgically created aortocaval fistulas.
- Administered lisinopril (3 mg/kg/day) and monitored hemodynamics, cardiac output (CO), renal blood flow (RBF), and plasma neurohormones.
- Sham-operated SHR served as controls.
Main Results:
- Lisinopril decreased left ventricular end-diastolic pressure (LVEDP) and prevented ascites in fistula rats.
- Treatment improved renal blood flow (RBF) and increased plasma renin activity (PRA).
- Survival was prolonged in lisinopril-treated fistula rats, with attenuated plasma norepinephrine (NE) levels.
Conclusions:
- Lisinopril ameliorates congestion and improves survival in HOHF without compromising cardiorenal hemodynamics.
- Venous and renal vasodilation, along with modulation of vasoconstrictive systems, likely contribute to beneficial effects.
- Lisinopril demonstrates therapeutic potential for high-output heart failure.
Abstract:
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.