Role of angiotensin II in the altered renal function of congestive heart failure.
Key result
Rats with myocardial infarction had reduced glomerular plasma flow rate (75 vs 165 nl/min, P<0.005), which was reversed by intravenous infusion of teprotide.
Why the study?
Does intravenous infusion of teprotide improve altered renal hemodynamics in rats with congestive heart failure post-myocardial infarction?
Population
Rats with extensive myocardial infarction produced by ligation of the left coronary artery 4 weeks prior to…
Comparison
Intravenous infusion of teprotide. vs Sham-operated control rats.
Design
Preclinical
Follow-up
4 weeks post-MI
Authors
Discussion
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Implication
ACE inhibition reverses post-MI renal hemodynamic changes in rats; leaves open translation to human heart failure.
Key Points
- To determine the role of angiotensin II in mediating renal cortical microcirculatory dynamics and tubular fluid reabsorption during congestive heart failure.
- Assessed glomerular and tubular function using micropuncture in rats 4 weeks after myocardial infarction induced by left coronary artery ligation versus sham-operated controls.
- Measured hemodynamic responses and fractional proximal fluid reabsorption before and during intravenous infusion of the angiotensin I-converting enzyme inhibitor teprotide.
- Infarcted rats exhibited lower mean arterial pressure (96 ± 5 vs. 122 ± 4 mm Hg, P < 0.005), higher left ventricular end-diastolic pressure (24 ± 3 vs. 5 ± 0 mm Hg, P < 0.001), and elevated efferent arteriolar resistance (3.03 ± 0.31 vs. 0.95 ± 0.16 × 10^10 dyn·sec·cm^-5, P < 0.001).
- Glomerular plasma flow declined significantly (75 ± 8 vs. 165 ± 17 nl/min, P < 0.005) with a smaller reduction in single nephron GFR (28.0 ± 2.8 vs. 41.7 ± 3.1 nl/min, P < 0.025), raising filtration fraction (0.38 ± 0.02 vs. 0.25 ± 0.02, P < 0.005) alongside elevated proximal fluid reabsorption (2.21 ± 0.12 vs. 1.64 ± 0.09, P < 0.025).
- Intravenous infusion of teprotide reversed efferent arteriolar resistance, single nephron filtration fraction, plasma flow, and fluid reabsorption back toward control values.
Structured PICO
Does intravenous infusion of teprotide improve altered renal hemodynamics in rats with congestive heart failure post-myocardial infarction?
P
Population
Rats with extensive myocardial infarction produced by left coronary artery ligation 4 weeks prior to study.
E
Exposure
Intravenous infusion of teprotide (an angiotensin I-converting enzyme inhibitor).
C
Comparator
Sham-operated control rats.
O
Outcome
Glomerular and tubule functions assessed by micropuncture (glomerular plasma flow rate, single nephron glomerular filtration rate, single nephron filtration fraction, efferent arteriolar resistance, fractional proximal fluid reabsorption).surrogate
Main Result
Absolute Event Rate: 75% vs 165%
p-value: p=<0.005
In a rat model of heart failure post-myocardial infarction, ACE inhibition with teprotide reversed altered renal hemodynamics, suggesting angiotensin II mediates the renal dysfunction in congestive heart failure.
Cite This Study
Ichikawa et al. (1984) studied Congestive heart failure / Myocardial infarction. Myocardial infarction vs. Sham-operated control rats was evaluated on Glomerular plasma flow rate (p=<0.005). Rats with myocardial infarction had reduced glomerular plasma flow rate (75 vs 165 nl/min, P<0.005), which was reversed by intravenous infusion of teprotide.