Vol. 281, Issue 5, F802-F809, November 2001
Simvastatin reverses impaired regulation of renal oxygen
consumption in congestive heart failure
Stephen
Adler1,
Harer
Huang1,
Jean Noel
Trochu2,
Xiaobin
Xu2,
Shabnam
Gupta1, and
Thomas H.
Hintze2
1 Division of Nephrology, Department of Medicine, and the
2 Department of Physiology, New York Medical College,
Valhalla, New York 10532
First published July 12, 2001;
10.1152/ajprenal.00138.2001.
Nitric oxide (NO) production by
endothelial nitric oxide synthase (eNOS) regulates renal O2
consumption. This mechanism is impaired in heart and kidney of dogs
with heart failure (CHF). Simvastatin, an inhibitor of
3-hydroxy-3-methylglutaryl-CoA reductase, increases eNOS expression in
the endothelium. Therefore, we studied whether simvastatin treatment
could restore the regulation of renal O2 consumption by
stimulators of NO production in dogs with CHF. Renal O2
consumption was measured after stimulation of NO production with
bradykinin, ramiprilat, or amlodipine or the NO donor
S-nitroso-N-acetylpenicillamine (SNAP).
Simvastatin delayed the time to euthanasia in dogs with CHF (35 ± 1.0 vs. 29 ± 1.2 days; P < 0.01). In normal
dogs, bradykinin (10
4 M), ramiprilat (104
M), amlodipine (105 M), and SNAP (104 M)
significantly reduced O2 consumption in the renal cortex
(
31.8 ± 0.9, 30.3 ± 1.1, 30.1 ± 2.0, 46.9 ± 1.0%) and renal medulla (29.7 ± 2.1, 33.0 ± 2.7, 30.8 ± 2.2, 46.8 ± 1.1%).
Responses to bradykinin, ramiprilat, and amlodipine were significantly
attenuated in CHF but were partially or completely restored by
simvastatin. Responses to SNAP were unaffected. These data demonstrate
that treatment with simvastatin improves renal production of NO in CHF,
restoring the normal regulation of renal O2 consumption by NO.
nitric oxide; renal physiology; endothelial nitric oxide synthase
