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Dysfunction of the cholinergic anti-inflammatory pathway mediates organ damage in hypertension
- Source :
- Hypertension (Dallas, Tex. : 1979). 57(2)
- Publication Year :
- 2010
-
Abstract
- Inflammatory responses are associated with the genesis and progression of end-organ damage (EOD) in hypertension. A role for the α7 nicotinic acetylcholine receptor (α7nAChR) in inflammation has recently been identified. We tested the hypothesis that α7nAChR dysfunction contributes to hypertensive EOD. In both spontaneously hypertensive rats (SHRs) and rats with abdominal aorta coarctation–induced hypertension, atropine-induced tachycardia was blunted compared with normotensive controls. Both models of hypertension were associated with deficits in expression of the vesicular acetylcholine transporter and the α7nAChR in cardiovascular tissues. In hypertension induced by abdominal aorta coarctation, deficits in aortic vesicular acetylcholine transporter and α7nAChR were present both above and below the coarctation site, indicating that they were independent of the level of arterial pressure itself. Hypertension in 40-week-old SHRs was associated with cardiac and aortic hypertrophy. Morphological abnormalities consistent with EOD, along with elevated tissue levels of proinflammatory cytokines (tumor necrosis factor-α, interleukin-1β, and interleukin-6) were observed in the heart, kidney, and aorta. Chronic treatment of SHRs with the α7nAChR agonist PNU-282987 relieved EOD and inhibited tissue levels of proinflammatory cytokines and activation of nuclear factor κB. Greater serum levels of proinflammatory cytokines and more severe damage in the heart, aorta, and kidney were seen in α7nAChR −/− mice subjected to 2-kidney-1-clip surgery than in wild-type mice. A deficit in the cholinergic anti-inflammatory pathway appears to contribute to the pathogenesis of EOD in models of hypertension of varying etiology. This pathway may provide a new target for preventing cardiovascular disease resulting from hypertension.
- Subjects :
- Atropine
Male
medicine.medical_specialty
alpha7 Nicotinic Acetylcholine Receptor
End organ damage
Multiple Organ Failure
Vesicular Acetylcholine Transport Proteins
Blotting, Western
Inflammation
Blood Pressure
Muscarinic Antagonists
Receptors, Nicotinic
Kidney
Rats, Inbred WKY
Proinflammatory cytokine
Rats, Sprague-Dawley
Bridged Bicyclo Compounds
Mice
medicine.artery
Internal medicine
Vesicular acetylcholine transporter
Rats, Inbred SHR
Internal Medicine
medicine
Animals
Cholinergic anti-inflammatory pathway
Aorta
Mice, Knockout
business.industry
Myocardium
NF-kappa B
medicine.disease
Rats
Microscopy, Electron
Blood pressure
Endocrinology
Hypertension, Renovascular
Benzamides
Cholinergic
medicine.symptom
Inflammation Mediators
business
Signal Transduction
Subjects
Details
- ISSN :
- 15244563
- Volume :
- 57
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Hypertension (Dallas, Tex. : 1979)
- Accession number :
- edsair.doi.dedup.....bf50059880e0559b18df2b1d1fd43cf7