Despite accumulating data of muscle sympathetic nerve activity (SNA) measured by human microneurography, whether neural discharges of muscle SNA correlates and coheres with those of other SNAs controlling visceral organs remains unclear. Further, how the baroreflex control of SNA affects the relations between these SNAs remains unknown. In urethane and α-chloralose anesthetized, vagotomized, and aortic-denervated rabbits, we recorded muscle SNA from the tibial nerve using microneurography and simultaneously recorded renal and cardiac SNAs. After isolating the carotid sinuses, we produced a baroreflex closed-loop condition by matching the isolated intracarotid sinus pressure (CSP) with systemic arterial pressure (CLOSE). We also fixed CSP at operating pressure (FIX) or altered CSP widely (WIDE: operating pressure ± 40 mmHg). Under these conditions, we calculated time-domain and frequency-domain measures of the correlation between muscle SNA and renal or cardiac SNAs. At CLOSE, muscle SNA resampled at 1 Hz correlated with both renal (r² = 0.71 ± 0.04, delay = 0.10 ± 0.004 s) and cardiac SNAs (r² = 0.58 ± 0.03, delay = 0.13 ± 0.004 s) at optimal delays. Moreover,muscle SNA at CLOSE strongly cohered with renal and cardiac SNAs(coherence >0.8) at the autospectral peak frequencies, and weakly (0.4–0.5) at the remaining frequencies. Increasing the magnitude of CSP change from FIX to CLOSE and further to WIDE resulted in corresponding increases in correlation and coherence functions at nonpeak frequencies, and the coherence functions at peak frequencies remained high (>0.8). In conclusion, muscle SNA correlates and coheres approximately with renal and cardiac SNAs under closed-loop baroreflex conditions. The arterial baroreflex is capable of potently homogenizing neural discharges of these SNAs by modulating SNA at the nonpeak frequencies of SNA autospectra.

View full abstract

Apoptosis is a major form of cell death that occurs in response to a variety of signals in both physiological and pathological situations. A hallmark of apoptosis is normotonic cell shrinkage, called apoptotic volume decrease (AVD), the process of which involves fluxes of K⁺, Cl⁻, and Na⁺. Na⁺ influx was suggested to be required in Fas-induced apoptosis in human Jurkat T cells, whereas Na⁺ efflux was found to be associated with AVD and apoptosis in human HL-60 cells. Here we examined the effects of extracellular Na⁺ deprivation on cell volume and viability in human epithelial HeLa cells. The incubation of HeLa cells in normotonic Na⁺-free Ringer solution resulted in persistent cell shrinkage after ≥30 min and reduction in cell viability after ≥1 h. After exposure to Na⁺-free solution for 5 h, a marked reduction in cell viability was found to be associated with an activation of caspase-3 without showing significant LDH release, indicating that the cells underwent apoptosis but not necrosis. Na⁺ deprivation-induced cell shrinkage and apoptotic cell death were significantly inhibited by a blocker of Na⁺-K⁺-2Cl⁻ cotransporter (NKCC) or of the reverse-mode operation of Na⁺/Ca²⁺ exchanger (NCX), but not by a blocker of Na⁺/H⁺ exchanger (NHE). Therefore it is concluded that Na⁺ deprivation causes persistent cell shrinkage resulting from Na⁺ efflux mainly via NKCC and NCX and thereafter leads to apoptotic death of HeLa cells. It is also suggested that normotonic cell shrinkage per se, if persistent, provides a sufficient condition for apoptosis induction.

View full abstract

The purpose of this study was to investigate whether nausea or gastric dysrhythmia, including tachygastria, which was determined by electrogastrography (EGG), were observed during optokinetic motion sickness in healthy Japanese volunteers. Twelve volunteers (9 men and 3 women) participated in the study. The subjects were asked to sit in a chair with their heads positioned in the center of a drum whose inside had been painted with black and white stripes. After a 15 min resting period, the drum was rotated at a speed of 60 degree/sec for 15 min. The EGG was continuously recorded for a total of 45 min (15 min resting period, 15 min rotation period, and 15 min recovery period). The severity of nausea was evaluated with a visual analogue scale (VAS) before, immediately after, and 15 min after the cessation of drum rotation. Other motion sickness symptoms were evaluated by scores of subjective symptoms of motion sickness (SSMS). Of 12 subjects who completed the study, 10 complained of nausea immediately after cessation of drum rotation. The VAS score for nausea immediately after the drum rotation period and 15 min after cessation of the rotation was significantly higher than during the resting period. The EGG during the drum rotation period showed a decrease in normogastria, which was accompanied with an increase in tachygastria. We conclude that gastric tachyarrhythmia and nausea may be induced by viewing an optokinetic rotating drum in healthy Japanese subjects who may have a hypersusceptibility to vection-induced motion sickness. The gastric dysrhythmia obtained with EGG could be a useful observation to support the appearance of nausea induced by optokinetic motion sickness.

View full abstract

The purpose of the present study was to examine the effect of unilateral lower limb suspension (ULLS) deconditioning on oxygen uptake kinetics. Eight healthy males underwent ULLS for 20 days and performed a series of 6-min square-wave transitions from rest to 60-W single-leg cycling exercises just before and after ULLS. To characterize the kinetics of the oxygen uptake response, a single exponential model was applied to the data until the end of the fast component omitted the first 15 s of the on-transit using a nonlinear least-squares fitting procedure. The following results were found: (i) the time constant of oxygen uptake was unchanged before and after ULLS; (ii) although there was no significant difference in the baseline and the asymptotic amplitude of the fast component, the asymptote, i.e., the absolute asymptotic amplitude of the fast component (the sum of the baseline and the asymptotic amplitude), and the end exercise oxygen uptake were decreased after ULLS; (iii) the contribution of the slow component to the total response of oxygen uptake was unchanged at pre- and post-ULLS. In conclusion, the asymptote in the fast component and the end exercise oxygen uptake were decreased after 20-d ULLS, though the response speed and the amplitude of the slow component of oxygen uptake were not changed. It is suggested that deconditioning as a result of limb disuse affects oxygen uptake response.

View full abstract

An electrophoretic protocol previously used for the separation of rat myosin heavy chain (MHC) isoforms was slightly modified to improve the separation of human MHC isoforms in both large and minigel systems. The addition of reducing agents (β-mercaptoethanol or dithiothreitol) to the top running buffer (TRB) radically improved separated MHC isoform resolution and the intensity of electrophoretic runs lasting longer than 5 h. In minigel systems, the MHC isoforms could be separated in as little as 5 h. The improved resolution of bands with the inclusion of reducing agents to the TRB facilitated the identification of clear boundaries for densitometric quantification of relative MHC isoform content, particularly for MHC IIa and MHC IIx. No significant effect of these reducing agents added to the TRB was observed for runs lasting only 100 min. Thus the inclusion of reducing agents in the TRB is essential for long electrophoretic runs, usually when separating large molecular mass proteins.

View full abstract

Peripheral vascular occlusive diseases are frequently observed in humans, and studies with animal models have been largely used. However the effects of sustained lower limb ischemia on normal and regenerating hindlimb skeletal muscles are not well known in the mouse model. Therefore prolonged unilateral hindlimb ligation was generated by femoral artery ligation. Normal (myotoxic-untreated) and regenerating (myotoxic-reated) ischemic muscles were studied by analyses of the in situ contractile properties and histological parameters. Concerning normal mouse muscles, we found that femoral artery ligation reduced hindlimb perfusion and altered muscle structure and function. Thus 7 days after ligation, maximal tetanic force was reduced by about 70%, (p < 0.05). By 56 days after ligation, muscle weights and cross-section areas of muscle fibers were still reduced (p < 0.05). Concerning myotoxic treated muscles, we report that ligation reduced the recovery of muscle weight and maximal tetanic force and increased fatigue resistance at 56 days (p < 0.05). In conclusion, our results demonstrate that sustained peripheral arterial insufficiency in mice induces long-term as well as acute detrimental effects in both normal and regenerating muscles.

View full abstract

This study was performed to investigate the heterogeneity of physiological and pharmacological properties in segments of the facial veins with special reference to selective brain cooling. Canine facial veins were isolated and the isometric tension of each segment was measured using the organ bath technique. Vessels in the segments of the facial veins that run opposite to the buccal cavity automatically produced myogenic tone and tended to show spontaneous contractions, but vessels in other segments did not. When no contractile agent was used for precontraction, noradrenaline and adrenaline produced dose-dependent relaxations in the former venous segments, but contractions in the latter ones. A Schild plot analysis for metoprolol against denopamine and for ICI118,551 against salbutamol showed that the venous segments running opposite the buccal cavity contained both β₁- and β₂-adrenoceptors, but the other venous segments contained only β₂-adrenoceptors. Electrical field stimulation-induced tetrodotoxin-sensitive relaxations in the former venous segments were diminished by pretreatment with metoprolol, but not with ICI118,551, indicating that the electrical stimulation–induced relaxation may be related to the activation of β₁-adrenoceptors in the venous smooth muscles. In conclusion, the heterogeneity of the functional properties, especially in the distribution of β-adrenoceptors, in different segments of canine facial veins was observed in the present study, and autoregulatory mechanisms, humoral mechanisms, and neural mechanisms were suggested to affect cranial venous drainage.

View full abstract

A high-salt diet reduced the levels of renal cAMP content and serine-phosphorylated paracellin-1 in Dahl salt-sensitive hypertensive rats. In MDCK cells expressing paracellin-1, protein kinase A inhibitor reduced the serine-phosphorylated paracellin-1 and transepithelial Mg²⁺ transport, suggesting that a dephosphorylation of paracellin-1 induces the reduction of Mg²⁺ reabsorption in salt-sensitive hypertension.

View full abstract

We used cytochalasin D to reduce contraction-related optical signals by inhibiting muscle contraction for the optical monitoring of action potentials, using a voltage-sensitive dye in isolated rat atrium preparations. The suppression of contraction-related signals was so strong that we concluded that this chemical is suitable for this purpose.

View full abstract

The neuronal activity of vestibulospinal neurons projecting to the lumbar enlargement was recorded in conscious rats standing with four limbs on a pitching platform. The neurons were classified into 3 groups: up-neurons firing maximally in the head-up phase (2/8), down-neurons with maximal firing in the head-down phase (2/8), and nonmodulated neurons (4/8). The 3 groups may play differential roles in stance control.

View full abstract