Background: Exercise therapy has shown significant efficacy as a means of treating various intestinal diseases, but its role in the treatment of constipation is still unclear. The purpose of this study was thus to analyze the effects of exercise on constipation by means of a systematic review and meta-analysis. Methods: PubMed, Web of Science, EMBASE, Cochrane Library and three Chinese databases [Wanfang Database, Chinese Biomedical Literature (CBM) and China National Knowledge Infrastructure (CNKI)] were searched for relevant studies published through June 2018. Eligible studies were selected in accordance with the PRISMA statement. The main results of interest were changes in gastrointestinal symptoms. Results: A total of nine randomized controlled trials involving 680 participants were included. Eight studies involved aerobic exercise and only one study involved anaerobic exercise. The aerobic exercises included were Qigong, walking and physical movement. The results of this systematic review and meta-analysis indicated that exercise had significant benefits as a means of improving the symptoms of constipation patients [relative risk (RR) = 1.97; 95% CI: 1.19, 3.27; p = .009; I²=91.3%]. Subgroup analyses showed that aerobic exercise (RR = 2.42; 95% CI: 1.34, 4.36; p = .000; I²=88%) similarly had a positive effect on constipation. However, these results were associated with a high risk of bias. Conclusion: Our results suggest that exercise may be a feasible and effective treatment option for patients with constipation. However, due to methodological shortcomings, the real effect of this intervention cannot be definitively determined. Researchers should, therefore, design more rigorous studies in order to evaluate the effect of exercise on constipation.

Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM) cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BK_Ca channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM) caused concentration-dependent inhibition of BK_Ca in VSM cells. Apelin-13 (0.1 µM) significantly decreased BK_Ca current density from 71.25±8.14 pA/pF to 44.52±7.10 pA/pF (n=14 cells, P<0.05). This inhibitory effect of apelin-13 was confirmed by single channel recording in cell-attached patches, in which extracellular application of apelin-13 (0.1 µM) decreased the open-state probability (NP_o) of BK_Ca channels in freshly isolated VSM cells. However, in inside-out patches, extracellular application of apelin-13 (0.1µM) did not alter the NP_o of BK_Ca channels, suggesting that the inhibitory effect of apelin-13 on BK_Ca is not mediated by a direct action on BK_Ca. In whole cell patches, pretreatment of VSM cells with LY-294002, a PI3-kinase inhibitor, markedly attenuated the apelin-13-induced decrease in BK_Ca current density. In addition, treatment of arteries with apelin-13 (0.1 µM) significantly increased the ratio of phosphorylated-Akt/total Akt, indicating that apelin-13 significantly increases PI3-kinase activity. Taken together, the data suggest that apelin-13 inhibits BK_Ca channel via a PI3-kinase-dependent signaling pathway in cerebral artery VSM cells, which may contribute to its regulatory action in the control of vascular tone.