September 1, 2001Hypertension
Differential Subcellular Actions of ACE Inhibitors and AT 1 Receptor Antagonists on Cardiac Remodeling Induced by Chronic Inhibition of NO Synthesis in Rats
Key result
ACE inhibitors and ARBs equally attenuated L-NAME-induced cardiac hypertrophy in rats by inhibiting p70S6K (2.2-fold activation by L-NAME) or ERK (1.8-fold activation), respectively.
Why the study?
Do ACE inhibitors and ARBs prevent cardiac remodeling in rats with L-NAME-induced NO synthesis inhibition?
Population
Wistar-Kyoto rats with cardiac hypertrophy induced by chronic inhibition of NO synthesis via L-NAME
Comparison
ACE inhibitors, ARBs, temocapril-CS866… vs Untreated control, D-NAME, L-NAME alone, or…
Design
Preclinical
Follow-up
8 weeks
Authors
Discussion
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Implication
Should not change clinical practice; hypothesis-generating for pathway-specific effects in NO-deficient hypertrophy models.
Structured PICO
Do ACE inhibitors and ARBs prevent cardiac remodeling in rats with L-NAME-induced NO synthesis inhibition?
P
Population
Wistar-Kyoto rats treated with NO synthase inhibitor L-NAME for 8 weeks to induce cardiac hypertrophy.
I
Intervention
ACE inhibitors (enalapril 3 mg/kg/d or temocapril 1 or 10 mg/kg/d), ARBs (losartan 10 mg/kg/d or CS-866 1 or 10 mg/kg/d), temocapril-CS866 combination (1 or 10 mg/kg/d), or rapamycin (0.5 mg/kg/d)
C
Comparator
Untreated control, D-NAME (inactive isomer), L-NAME alone, or L-NAME plus hydralazine
O
Outcome
Ratios of coronary wall to lumen (wall/lumen) and left ventricular weight to body weight (LVW/BW), and activation of p70S6K and ERK in myocardiumsurrogate
ACE inhibitors and ARBs reduce cardiac hypertrophy through different intracellular signaling pathways (p70S6K and ERK, respectively) in a rat model of chronic NO inhibition.
Cite This Study
Sanada et al. (2001) studied Cardiac hypertrophy. ACE inhibitors (enalapril, temocapril) and ARBs (losartan, CS-866) vs. L-NAME alone, untreated control, L-NAME plus hydralazine was evaluated on Ratios of coronary wall to lumen and left ventricular weight to body weight. ACE inhibitors and ARBs equally attenuated L-NAME-induced cardiac hypertrophy in rats by inhibiting p70S6K (2.2-fold activation by L-NAME) or ERK (1.8-fold activation), respectively.