Abstract
Autonomic dysfunction and abnormal immunity lead to systemic inflammatory responses, which result in cardiovascular damage in hypertension. The aim of this report was to investigate the effects of choline on cardiovascular damage in hypertension. Eight-week-old male spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were intraperitoneally injected with choline or vehicle (8 mg/kg/day). After 8 weeks, choline restored the cardiac function of the SHRs, as evidenced by decreased heart rate, systolic blood pressure, left ventricle systolic pressure, and ±dp/dtmax and increased ejection fraction and fractional shortening. Choline also ameliorated the cardiac hypertrophy of the SHRs, as indicated by reduced left ventricle internal dimensions and decreased cardiomyocyte cross-sectional area. Moreover, choline improved mesenteric arterial function and preserved endothelial ultrastructure in the SHRs. Notably, the protective effect of choline may be due to its anti-inflammatory effect. Choline downregulated expression of interleukin (IL)-6 and tumour necrosis factor-α and upregulated IL-10 in the mesenteric arteries of SHRs, possibly because of the inhibition of Toll-like receptor 4. Furthermore, choline restored baroreflex sensitivity and serum acetylcholine level in SHRs, thus indicating that choline improved vagal activity. This study suggests that choline elicits cardiovascular protective effects and may be useful as a potential adjunct therapeutic approach for hypertension.
Highlights
These deficits appear to contribute to the pathogenesis of end-organ damage in hypertension
The results of the present study provide the first evidence that choline treatment alleviates cardiovascular damage and slows the progression of hypertension possibly via the improvement of vagal activity and inhibition of the vascular inflammatory response in spontaneously hypertensive rats (SHRs)
The salient findings of this study are as follows: (1) SHRs displayed a series of significant characteristics, such as low vagal activity, high blood pressure, target-organ damage and cardiac hypertrophy; (2) choline treatment attenuated the development of hypertension, reduced heart rate and prevented hypertension-associated cardiac, renal and vascular damages; (3) these cardiovascular protective effects of choline were related to the inhibition of Toll-like receptor 4 (TLR4) and pro-inflammatory cytokines (IL-6, TNF-α)and the upregulation of anti-inflammatory cytokine IL-10; and (4) choline significantly increased Baroreflex sensitivity (BRS) and serum ACh levels, indicating that choline elevated vagal activity
Summary
These deficits appear to contribute to the pathogenesis of end-organ damage in hypertension. A recent study showed that chronic vagal nerve stimulation alleviates hypertension-induced endothelial dysfunction and aortic stiffening in stroke-prone SHRs20. Our recent studies have shown that choline exhibits a remarkable protective effect against ischaemia/reperfusion-induced vascular damage in rats by inhibiting the reactive oxygen species-mediated Ca2+/calmodulin-dependent protein kinase II pathway and regulating Ca2+-cycling proteins[26]. The effects of choline on the inflammatory response and vagal activity, two important factors in hypertension, have not been characterized in SHRs. in the present study, we sought to investigate the effects of choline on vagal activity in hypertension, as proposed in a recent presentation by the authors[27]. The role of choline in inhibiting the inflammatory response and ameliorating cardiovascular damage in SHRs is explored here
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