Premium
Effect of cholinesterase inhibitor neostigmine on overload‐induced cardiac hypertrophy and pro‐ and anti‐inflammatory cytokines
Author(s) -
Li YiFan,
Freeling Jessica,
Wattier Kristina,
LaCroix Carly
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1204-b
Subject(s) - medicine , heart failure , endocrinology , saline , cytokine , heart rate , muscle hypertrophy , pressure overload , blood pressure , cardiac hypertrophy
Enhancement of parasympathetic nerve activity exerted beneficial effect on congestive heart failure (CHF). However, the underlying mechanisms remain to be determined. The present study was to investigate if this beneficial effect involves regulation of pro‐ and anti‐inflammatory cytokines in the heart. Transverse aortic constriction (TAC)‐induced cardiac hypertrophy and dysfunction in rats was used in the present study. To augment parasympathetic activity, a low dose of a peripheral cholinesterase inhibitor, neostigmine (Neo, 0.01 mg/kg per day) was injected subcutaneously for two weeks in TAC and sham rats. There was a slight decrease in heart rate in Neo treated group (318±25 bpm), compared with saline group (341±23 bpm), indicating an increase in parasympathetic control of the heart. The ratios of heart weight vs. body weight were 3.46±0.10 in TAC‐Neo group and 4.47±0.45 in TAC‐saline group, suggesting a significant reduction in TAC‐induced cardiac hypertrophy by Neo. Neo also improved elevated left ventricular end‐diastolic pressure induced by TAC. Moreover, the protein level of pro‐inflammatory cytokine TNFα was decreased in heart tissues in the TAC rats treated with Neo compared with saline control. In contrast, the level of anti‐inflammatory cytokine IL‐10 was increased in the TAC rats treated with Neo. These data suggest that augmentation of parasympathetic activity exerts cardiac protection at least partly via regulation of the productions of pro‐ and anti‐inflammatory cytokines in the heart. Supported by American Heart Association Beginning Grant‐in Aid No. 0460063Z, NIH INBRE Grant No. 2 P20 RR016479, and NIH COBRE grant No. 5 P20 RR017662