Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure.
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Why the study?
Does enalapril attenuate the activation of intrarenal angiotensinogen mRNA expression in rats with chronic stable experimental heart failure?
Population
Male Sprague-Dawley rats with stable compensated heart failure 12 weeks after experimental myocardial…
Comparison
Enalapril 25 mg/kg per day administered orally… vs Vehicle-treated heart failure rats and…
Design
Preclinical, Investigators were blinded for the operation during all…
Follow-up
12 weeks
Authors
Discussion
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Implication
Hypothesis-generating for intrarenal RAS in experimental HF; leaves open clinical translation and human validation.
Key Points
- To evaluate circulating renin-angiotensin system components alongside intrarenal renin and angiotensinogen mRNA expression in rats with chronic stable heart failure following myocardial infarction.
- Evaluated rats 12 weeks after experimental myocardial infarction or sham surgery, comparing vehicle-treated heart failure rats against sham controls.
- Administered enalapril (25 mg/kg per day) in drinking water for 6 weeks in a parallel heart failure cohort (n=11).
- Measured circulating renin-angiotensin system components, renal angiotensin II concentrations, liver angiotensinogen mRNA, and intrarenal renin and angiotensinogen mRNA.
- Renal angiotensinogen mRNA increased by 47% in vehicle-treated heart failure rats compared to sham controls (P = 0.001), showing greater increases in medium (46%, P < 0.05) and large (66%, P < 0.05) infarcts, while intrarenal angiotensin II rose twofold (P < 0.05).
- Circulating angiotensinogen, angiotensin II, plasma renin concentration, liver angiotensinogen mRNA, and renal renin mRNA showed no significant differences between vehicle-treated heart failure and sham control rats.
- Enalapril treatment reduced blood pressure (91 vs. 103 mm Hg, P < 0.05), increased plasma renin concentration 15.5-fold (P < 0.005), and attenuated the heart failure-induced increase in renal angiotensinogen mRNA (P < 0.001).
Structured PICO
Does enalapril attenuate the activation of intrarenal angiotensinogen mRNA expression in rats with chronic stable experimental heart failure?
P
Population
Male Sprague-Dawley rats (200-250 g, 2 months of age) with stable compensated heart failure 12 weeks after experimental myocardial infarction (left coronary artery ligation) or sham operation.
I
Intervention
Enalapril 25 mg/kg per day administered orally in drinking water for 6 weeks.
C
Comparator
Vehicle-treated heart failure rats and sham-operated control rats.
O
Outcome
Renal angiotensinogen mRNA expression level.surrogate
In a rat model of chronic stable heart failure, the intrarenal renin-angiotensin system is activated independently of the circulating system, and this local activation is attenuated by ACE inhibition.
Cite This Study
Schunkert et al. (1992) studied this question.
Topics
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