Choline ameliorates cardiovascular damage by improving vagal activity and inhibiting the inflammatory response in spontaneously hypertensive rats

Figures

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  Figure 1. Choline attenuated the development of hypertension, improved cardiac function, and increased BRS and serum ACh level in SHRs. (a) SBP for eight weeks measured by tail cuff. (b) SBP, (c) MAP, (d) DBP, (e) LVSP & LVEDP, (f) ±dp/dtmax and (g) HR were measured by polygraph recorder at the end of the experiment. (h) The vagal activity index, BRS. (i) The concentration of ACh level in serum. Data are mean ± SEM (n = 8). *P < 0.05, **P < 0.01, ***P < 0.001 vs WKY. #P < 0.05, ##P < 0.01, ###P < 0.001 vs SHR. &P < 0.05, &&P < 0.01, &&&P < 0.001 vs SHR+Choline.

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  Figure 2. Choline attenuated cardiac hypertrophy in SHRs. (a) Representative H&E staining of cardiac cross-section. (b) Quantification of cross-sectional areas of the cardiomyocytes. (c) Quantification of cross-sectional areas of the cardiomyocytes. (d) The ratio of HW/BW. (e) The ratio of LVW/BW, Scale bar = 30 μm. Data are mean ± SEM (n = 8). *P < 0.05, **P < 0.01, ***P < 0.001 vs WKY; #P < 0.05, ##P < 0.01 vs SHR; &P < 0.01 vs SHR+Choline.

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  Figure 3. Choline attenuated renal damage in SHRs (a) Representative renal section with H&E staining in the experimental groups, arrows indicate glomeruli, scale bar = 50 μm. (b) The renal damage scores. Data are mean ± SEM (n = 8). ***P < 0.001 vs WKY; #P < 0.05 vs SHR; &P < 0.01 vs SHR+Choline.

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  Figure 4. Choline ameliorated the endothelial damage in SHRs. (a) Representative transmission electron micrographs of mesenteric artery. Arrows indicate endothelial cells. Scale bar = 2 μm. (b) Light microscopy image of H&E stained mesenteric artery and thoracic aorta, Scale bar = 10 μm. Arrows indicate endothelial cells. (c) Effects of choline on the concentration-response curves of mesenteric artery rings to 5-HT, PE, ACh and SNP in the mesenteric artery rings of WKY group (black), WKY+Choline group (blue), SHR group (red), SHR+Choline group (green) respectively. Data are mean ± SEM (n = 8). **P < 0.01, ***P < 0.001 vs WKY group; #P < 0.05 vs SHR group.

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  Figure 5. Western blot results of the expression of TLR4 protein and inflammatory cytokines in mesenteric arteries. (a) Protein expression of TLR4. (b) Protein expression of IL-6. (c) Protein expression of IL-10. (d) Protein expression of TNF-α. Data are mean ± SEM (n = 6). **P < 0.01, ***P < 0.001 vs WKY group; #P < 0.05, ##P < 0.01 vs SHR group. Full-length blots are presented in Supplementary Figure 5a–d.

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  Figure 6. The putative schematic illustration of the mechanism underlying choline-elicited cardiovascular protection in hypertension. SHRs displayed a series of significant characteristics, including low vagal activity, high blood pressure, cardiovascular damage and cardiac hypertrophy. Choline reduced cardiac hypertrophy by decreasing the LVM/BW, HW/BW, LVIDd(s), EDV, ESV, LVPW and cardiomyocyte cross-sectional area in SHRs. Choline restored cardiac function by decreasing ±dp/dtmax, LVSP, HR, and CO and increasing LVEF and LVFS in SHRs. Moreover, choline prevented vascular dysfunction and abnormal structure changes, possibly by reducing expression of TLR4, IL-6 and TNF-α and upregulating IL-10 in SHRs. These cardiovascular protective effects of choline may be attributed to the improvement of vagal activity and the inhibition of inflammatory responses. ACh, acetylcholine; BRS, baroreflex sensitivity; BW, body weight; CO, cardiac output; EDV, end diastolic volume; ESV, end-systolic volume; LV, left ventricle; LVEF, LV ejection fraction; LVFS, LV fractional shortening; LVIDd, LV internal dimension in diastole; LVIDs, LV internal dimension in systole; LVM, left ventricular mass; LVPW, the…