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Objective: Uric acid is supposed but not yet determined to be associated with atherosclerosis. Uric acid is released from damaged cells to form urate crystal, which is recognized by the immune system to produce IL (interleukin)-1. Danger signals and IL-1 have been shown to play an important role in atherosclerosis. We determined whether the physiological level of soluble uric acid promotes inflammation and develops atherosclerosis. Approach and Results: The secretion of IL-1β from human peripheral blood mononuclear cells mediated by NLRP3 (NACHT, LRR, and PYD domain-containing protein 3) inflammasome was promoted by physiological levels in serum uric acid. This augmentation of inflammation was mediated by the regulation of the AMPK (AMP-activated protein kinase)-mTOR (mammalian target of rapamycin) mitochondrial reactive oxygen species and HIF-1α (hypoxia-inducible factor-1α) pathway. In both of uricase transgenic and xanthine oxidase inhibitor–treated mice, decreased levels of uric acid resulted in the activation of AMPK and attenuation of the development of atherosclerotic plaques. Further, acute uric acid reduction by the administration of benzbromarone in healthy humans for 2 weeks significantly decreased plasma IL-18—an inflammasome-dependent cytokine. Conclusions: The data indicate that the development of atherosclerosis and inflammation is promoted by uric acid in vivo. Moreover, the lowering of uric acid levels attenuated inflammation via the activation of the AMPK pathway. This study provides mechanistic evidence of uric acid–lowering therapies for atherosclerosis.

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This method allows repeated, direct access to the immobilized muscle, making it a useful procedure for concurrent application and assessment of various therapeutic interventions. Muscle Nerve 54: 788-791, 2016.

We aimed to examine the afferent mechanisms for the reflex inhibition of the rhythmic micturition contractions (RMCs) of the urinary bladder induced by stimulation of the perineal skin afferents in urethane-anesthetized rats. Electrical stimulation (pulse duration: 0.5 ms) was applied to the cutaneous branches of the pudendal nerve (CBPN) at frequencies of 0.1, 1, and 10 Hz for 1 min. Nerve fiber groups were defined by recording compound action potentials from CBPN. Activation of only Aβ fibers (0.2 V) produced an inhibition of RMCs at 7–11 min after the onset of stimulation (late inhibition), at any tested frequency. Additional activation of Aδ fibers (1 V) produced additional early inhibition (immediately after stimulation) at 1 and 10 Hz. Furthermore, additional activation of C fibers (10 V) at 10 Hz completely stopped RMCs for >10 min. This strong inhibition persisted after local application of capsaicin to the stimulating CBPN. We conclude that activities of Aβ, Aδ, and C afferent fibers, without capsaicin-sensitive channels, can contribute to the inhibition of bladder contractions.

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Loss of skeletal muscle mass has a profound effect on daily life for the elderly and patients with serious diseases. We hypothesized that acupuncture is an alternative strategy for preventing skeletal muscle atrophy. In this study, we investigated the effect of acupuncture on two different mouse models of skeletal muscle atrophy: hindlimb suspension (HS) and spiral wire immobilization (SWI). Acupuncture was performed on the gastrocnemius muscle for 30 minutes every day. Muscle wet weight was significantly reduced by HS for two weeks. The HS‐induced reduction in muscle mass was significantly increased by acupuncture intervention in soleus. The mRNA expression levels of atrogin‐1/MAFbx and MuRF1, which play a principal role in muscle‐specific degradation as E3 ubiquitin ligases, were significantly increased by HS. Those were significantly decreased by acupuncture intervention compared to the HS group. In a protein synthesis pathway, the expression levels of Akt1 and TRPV4 mRNAs were significantly increased by acupuncture compared to the HS group. Muscle wet weight was significantly reduced by SWI for five days. The SWI ‐induced reduction was significantly increased by acupuncture intervention compared to the SWI group in soleus. These results indicate that acupuncture treatment may have an ameliorated effect on skeletal muscle atrophy through both protein synthesis and degradation pathways.