Author + information
- Longzhu Liu,
- Xi He,
- Yi Lu,
- Xiaojiang Yu and
- Weijin Zang
Autonomic dysfunction (sympathetic activation and vagal withdrawal) and abnormal immunity lead to continuous systemic inflammatory responses in target organs, which would result in cardiovascular damage in hypertensive patients. Previous studies demonstrated that choline improved cardiac function and reduced ischaemia/reperfusion-induced vascular damage, thus exerting cardiovascular protective effects as an M3 cholinoceptors agonist. However, whether it could improve cardiovascular damage by improving vagal activity and reducing inflammatory responses in hypertension is unclear. Therefore, this study investigates the role and underlying mechanism of choline in cardiovascular damage in spontaneously hypertensive rats (SHRs).
7∼8-week-old male SHRs and Wistar-Kyoto (WKY) rats were injected with choline chloride or saline intraperitoneally (8mg/kg/day) for 8 weeks. The blood pressure, the marker of vagal activity baroreflex sensitivity (BRS), acetylcholine (ACh) level in serum, the cardiac function and hemodynamic parameters (echocardiograph and powerlab), vascular endothelial damage (hematoxylin-eosin staining, transmission electron microscopy and myograph) and the expressions of inflammatory cytokines in arteries (western blot) were evaluated.
(1) Choline markedly attenuated systolic, diastolic, and mean arterial pressures in SHRs. (2) The ACh level in serum and BRS were decreased in SHRs, whereas treatment with choline improved BRS and ACh level. (3) Choline restored cardiac function by decreasing the heart rate, left ventricle systolic pressure, ±dp/dt, and increasing the ejection fraction, fractional shortening in SHRs.(4) The endothelial cells of mesenteric arteries were desquamated and the elastic membranes were fragmented in SHRs. Treatment with choline ameliorated the endothelial damage. (5) Choline significantly reduced the maximum contractile response to phenylephrine and 5-hydroxy tryptamine and enhanced the maximum ACh-induced vasorelaxation in SHRs, and the relaxations to sodium nitroprusside were not modified indicating choline improved endothelial function. (6) Choline not only prevented the increase in pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, but also upregulated IL-10 expression in mesenteric arteries in SHRs, which may be related to the inhibition of Toll like receptor 4 (TLR4).
The cardiovascular protective effects of choline may be attributed to the improvement of vagal activity and inhibition of TLR4-mediated inflammatory responses to ameliorate cardiovascular damage. Choline increased vagal activity, and thereby improved the neuroimmunoregulation in hypertension, which would help to provide novel therapeutic strategies for the protection against cardiovascular damage caused by hypertension.