Polyunsaturated fatty acids in heart failure.

progression of HF.10 Vagus stimulation reverses ventricular remodeling of the failing heart. Increasing parasympathetic activity stimulates endothelial nitric oxide generation. Right vagus stimulation in patients with advanced HF is feasible and safe and the consequent increased vagal tone improves the symptoms of HF and significantly increases the left ventricular ejection fraction. Acetylcholine, the principal vagal neurotransmitter, is a potent antiinflammatory molecule.11 These results suggest that activating antiinflammatory pathways in the form of vagal nerve stimulation is of benefit in CAD, HF and other inflammatory conditions.1,3,8,9 Secondary hypertension induces downregulation of the α7 nicotinic acetylcholine receptor (α7nAChR) and decreased expression of α7nAChR contributed to inflammation in the 2-kidney 1-clip hypertensive rat model, suggesting that hypertension is also a low-grade systemic inflammatory condition12 in which vagal tone is reduced.13 Because acetylcholine and LXs, resolvins and protectins have antiinflammatory actions, it is likely that acetylcholine and vagal nerve stimulation augment the production of LXs, resolvins and protectins and thus bring about their antiinflammatory actions. This is supported by the observation that a linoleic acid derivative, DCP-LA, ameliorated the learning and memory impairment by targeting the α7nAChR14 and that PUFAs enhance acetylcholine levels in the brain and other tissues.15,16 Hence, studying the roles of LXs, resolvins, protectins and acetylcholine and vagal tone in the pathobiology of CAD and HF may prove to be interesting.