[2006] [P2915] Chronic
therapy with electric Vagus Nerve stimulation normalizes mRNA and protein
expression of nitric oxide synthase in myocardium of dogs with heart
failure
R.C. Gupta, S. Mishra, S. Rastogi, M.
Imai, V. Zaca, H.N. Sabbah. Henry Ford Health System, Medicine, Detroit,
United States of America
Background:
Endothelial nitric oxide synthase (eNOS) is decreased in heart failure
(HF), a maladaptation that leads to the release of pro-inflammatory
cytokines and to cardiomyocytes apoptosis. Neuronal NOS (nNOS) and
inducible NOS (iNOS) are increased in HF. The latter is partly responsible
for the reduced responsiveness of the failing myocardium to exogenous
catecholamines. We previously showed that chronic (3 months) therapy with
electric Vagus nerve stimulation (VNS) using the CardioFit System
(BioControl Medical, Ltd.), improves LV function in dogs with
microembolization-induced HF. This study examined the effects of VNS on
mRNA and protein expression of eNOS, iNOS and nNOS and the nitrate +
nitrite pool (NNP = end product of nitric oxide, NO) in LV myocardium of
VNS-treated HF dogs.
Methods: RNA was extracted and homogenate
was prepared from LV tissue of 7 VNS-treated dogs, 6 HF control dogs and 6
normal (NL) dogs. mRNA expression of eNOS, iNOS, and nNOS was measured
using reverse transcriptase polymerase chain reaction and protein
expression was measured by Western blotting. Bands were quantified in
densitometric units (du).
Results: The data are shown in the
table. mRNA and protein expression of eNOS decreased and that of iNOS and
nNOS increased significantly in HF-controls compared to NL. VNS therapy
normalized mRNA and protein expression of all 3 NOS subtypes. NNP
decreased in HF-controls compared to NL (32 ± 3 vs. 57 ± 2 pmols/gram,
p<0.05) and significantly increased with VNS therapy (41 ± 2
pmols/gram) compared to HF-controls (p<0.05).
| NL | HF-Controls | HF + VNS | |
|---|---|---|---|
| eNOS mRNA (du) | 1.44 ± 0.15 | 0.51 ± 0.02* | 0.90 ± 0.03† |
| eNOS Protein (du) | 74.2 ± 5.0 | 24.8 ± 3.0* | 58.3 ± 4.0† |
| iNOS mRNA (du) | 1.68 ± 0.15 | 4.05 ± 0.14* | 2.69 ± 0.28† |
| iNOS Protein (du) | 6.6 ± 0.6 | 29.7 ± 1.3* | 8.4 ± 0.4† |
| nNOS mRNA (du) | 1.55 ± 0.11 | 4.41 ± 0.52* | 1.98 ± 0.20† |
| nNOS Protein (du) | 10.4 ± 0.4 | 60.3 ± 2.4* | 19.5 ± 0.9† |
*=p<0.05 vs. NL; †=p<0.05 vs. HF-Controls
Conclusions: Long-term VNS therapy with CardioFit normalizes mRNA and protein expression of NOS in LV myocardium of dogs with HF and enhances NO production. This finding may explain, in part, the observed improvement in LV function in HF dogs chronically treated with VNS.
Session Info: Poster session 4
Citation: Eur Heart J 2006, 27(Abstract Suppl), 477