Calcitriol ameliorated autonomic dysfunction and hypertension by down-regulating inflammation and oxidative stress in the paraventricular nucleus of SHR.

The hypothalamic paraventricular nucleus (PVN) plays crucial roles in central cardiovascular regulation. Increasing evidence in humans and rodents shows that vitamin D intake is important for achieving optimal cardiovascular function. The purpose of this study was to investigate whether calcitriol, an active form of vitamin D, improves autonomic and cardiovascular function in hypertensive rats and whether PVN oxidative stress and inflammation are involved in these beneficial effects. Male spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were treated with either calcitriol (40 ng/day) or vehicle (0.11 µL/h) through chronic PVN infusion for 4 weeks. Blood pressure and heart rate were recorded continuously by radiotelemetry. PVN tissue, heart and plasma were collected for molecular and histological analysis. Compared to WKY rats, SHR exhibited increased systolic blood pressure, sympathetic drive, and cardiac hypertrophy and remodeling. These were associated with higher mRNA and protein expression levels of high mobility box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), proinflammatory cytokines, NADPH oxidase subunit in the PVN. In addition, increased norepinephrine in plasma, elevated reactive oxygen species levels and activation of microglia in the PVN were also observed in SHR. Chronic calcitriol treatment ameliorated these changes but not in WKY rats. Our results demonstrate that chronic infusion of calcitriol in the PVN ameliorates hypertensive responses, sympathoexcitation and retains cardiovascular function in SHR. Reduced inflammation and oxidative stress within the PVN are involved in these calcitriol-induced effects.

Irisin lowers blood pressure by activating the Nrf2 signaling pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

Exercise training is one of the major non-pharmacological treatments for hypertension. However, the central mechanism by which exercise training attenuates the hypertensive responses remains unclear. Irisin is a muscle-secreted cytokine derived from fibronectin type III domain containing 5 (FNDC5) that will be released into the circulation during exercise. We hypothesized that irisin may play a role in the blood pressure regulation by exercise. To examine the hypothesis, our study investigated the effect of irisin on hypertension and its central mechanism. The study was performed in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats. We found that intravenous injection of irisin effectively reduced blood pressure, plasma norepinephrine, paraventricular nucleus (PVN) levels of neuronal activation, oxidative stress and inflammation in SHRs. Moreover, irisin activated nuclear factor E2-related factor-2 (Nrf2) and restored the imbalance of neurotransmitters in the PVN. Our study also found PVN knockdown of Nrf2 abolished the protective effects of irisin on hypertension. These findings demonstrate irisin can improve hypertension via Nrf2-mediated antioxidant in the PVN.

[Clinical study of treating knee osteoarthritis (Bi syndrome of knee) by massage combined Chinese materia medica footbath fumigation and washing].

OBJECTIVE: To evaluate the clinical efficacy of treating knee osteoarthritis (KOA, Bi syndrome of knee) by massage combined Chinese materia medica (CMM) footbath fumigation and washing, and to observe the changes of the Lysholm knee score (LKSS). METHODS: Totally 61 patients with grade I to III KOA were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were treated with massage combined CMM footbath fumigation and washing, while those in the control group were treated with oral administration of meloxicam. They were treated for 20 days (times). The LKSS was assessed before treatment, 10 days of treatment, by the end of the treatment, and 1 month after treatment. RESULTS: (1) The therapeutic efficacy in the treatment group was superior to that in the control group (P < 0.05). Thirteen cases were clinically controlled, with 11 markedly effective, 6 effective, and 1 ineffective in the treatment group, while 5 cases were clinically controlled, with 11 markedly effective, 10 effective, and 4 ineffective in the control group. (2) The LKSS: The post-treatment LKSS was higher than that before treatment in the two groups. The LKSS at 10 days (times) of treatment was lower in the treatment group than in the control group, but with no statistical difference (P > 0.05). The LKSS by the end of the treatment was higher in the treatment group than in the control group (P < 0.05). (3) The case number of patients in need of receiving the treatment again within 1-month follow-up and the difference between the LKSS at follow-ups and that by the end of the treatment were lower in the treatment group than in the control group (P < 0.01). CONCLUSION: Massage combined CMM footbath fumigation and washing had better clinical efficacy on patients suffering from KOA.