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Chronic captopril and losartan (DuP 753) administration in rats with high-output heart failure
1Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.
Insights
Losartan and captopril treatments improved heart failure in rats with aortocaval shunts by normalizing blood pressure and reducing cardiac hypertrophy. These interventions also restored atrial natriuretic factor (ANF) levels, indicating a beneficial effect on the renin-angiotensin system.
Area of Science:
- Cardiovascular Physiology
- Renal Physiology
- Pharmacology
Background:
- Aortocaval (AC) shunts induce high-output heart failure in rats, characterized by altered hemodynamics and cardiac remodeling.
- The renin-angiotensin system (RAS) and atrial natriuretic factor (ANF) play crucial roles in regulating cardiovascular function during heart failure.
Purpose of the Study:
- To investigate the roles of ANF and RAS in AC shunt-induced heart failure.
- To evaluate the therapeutic effects of losartan (angiotensin II receptor antagonist) and captopril (ACE inhibitor) on hemodynamic parameters, cardiac hypertrophy, and ANF levels in rats with AC shunts.
Main Methods:
- Rats with AC shunts were treated with captopril or losartan.
- Hemodynamic parameters (mean arterial pressure, LVEDP), cardiac hypertrophy, plasma and tissue ANF levels, hematocrit, and urinary volume were measured.
- Comparisons were made between treated AC shunt rats, untreated AC shunt rats, and sham-operated controls.
Main Results:
- AC shunt rats exhibited elevated LVEDP, reduced MAP, cardiac hypertrophy, altered ANF distribution, and lower hematocrit.
- Both captopril and losartan treatments normalized LVEDP, decreased MAP, and significantly reversed cardiac hypertrophy.
- Plasma ANF levels tended to normalize in treated groups; losartan treatment decreased plasma COOH-terminal ANF and increased urinary volume and hematocrit.
Conclusions:
- Chronic blockade of the RAS with ACE inhibitors or angiotensin II receptor antagonists effectively improves hemodynamic conditions in rats with high-output heart failure.
- These treatments reverse cardiac hypertrophy and normalize water retention.
- RAS inhibition restores plasma and tissue ANF levels towards normal, highlighting the interplay between these systems in heart failure pathophysiology.
Abstract:
We investigated the role of atrial natriuretic factor (ANF) and the renin-angiotensin system as well as the effects of losartan in rats with aortocaval (AC) shunts. Right atrial and left ventricular end-diastolic pressures (LVEDP) were higher and mean arterial blood pressure (MAP) was lower in AC shunt animals than in their controls. AC shunt rats presented marked cardiac hypertrophy, decreased right atrial ANF concentration, and increased ventricular ANF content and concentration. Plasma ANF levels were elevated, and hematocrit was lower in AC shunt animals than in controls. Captopril or losartan treatment decreased MAP and returned LVEDP to sham-operated control values. A clear regression of cardiac hypertrophy was evident in both treated AC shunt groups, with plasma ANF levels tending to follow those in sham-operated rats. Plasma COOH-terminal ANF levels were decreased and urinary volume and hematocrit were increased in losartan-treated AC shunt animals. We conclude that chronic angiotensin converting enzyme inhibition and angiotension II receptor antagonism improved hemodynamic conditions, diminished water retention, reversed cardiac hypertrophy, and restored plasma and tissue ANF to more "normal" levels in rats with moderate high-output heart failure.