We investigated the effects of repeated eccentric exercise for rat medial gastrocnemius muscle on ankle joint stiffness and muscle connectin (titin) isoform composition (longer form, α-connectin; shorter form, β-connectin). Male Wistar rats were trained on a custom-made, isokinetic dynamometer (eccentric-exercise group, n = 6; sham-operated group, n = 6). The exercise session consisted of 20 eccentric contractions elicited by submaximal electric stimulations under anesthesia. The contracting muscle was forcibly lengthened by an isokinetic dorsi-flexion of the ankle joint (velocity, 30°/s; range of motion, 45°). Rats in the eccentric-exercise group were trained every two days for 20 days (10 sessions in total). The static passive resistive torque (PRT) of 45° at the ankle joint was used as a measure of the joint stiffness, and was determined before and after the experimental period. After 10 sessions of eccentric exercise, the wet weight of medial gastrocnemius muscle significantly increased (P < 0.05), whereas the static PRT significantly decreased (P < 0.05) in the eccentric-exercise group, when compared to the sham-operated group. Myosin-ATPase staining showed a decrease in the number of type IIb/IId fibers (P < 0.001) and an increase in the number of type IIa fibers (P < 0.05). However, no significant difference was seen in the connectin (titin) isoform composition between the eccentric-exercise group and the sham-operated group, suggesting that the reduction in PRT was not due to change in resting mechanical properties of muscle fibers.

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Clenbuterol, a β-adrenoceptor agonist, has been reported to induce skeletal muscle hypertrophy. However, it has also been known to reduce aerobic exercise performance and to deleteriously affect endurance and sprint exercise performance in rats. In the present study, the chronic administration of clenbuterol (2 mg/kg body weight; 30 days) resulted in various ultrastructural changes in three different types of muscles, gastrocnemius, a mixed-fiber type; anterior latissimus dorsi (ALD), a predominantly fast-twitch type; and diaphragm, a largely oxidative-type. The most prominent changes included mitochondrial swelling, matricular vesiculation in mitochondria, mitochondrial hyperplasia, sarcoplasmic vesiculation, and intermyofibrillar dilations. An increase in the cross-sectional area of both the subsarcolemmal (170, 167, and 79%) and the intermyofibrillar (129, 134, and 84%) mitochondria is noticed in the gastrocnemius, ALD, and diaphragm, respectively. The ultramicroscopic and morphometric results suggest drug-induced defects in contractile and oxidative activities.

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The effect of CO₂/HCO₃⁻ on the endocochlear potential (EP) was examined by using both ion-selective and conventional microelectrodes and the endolymphatic or perilymphatic perfusion technique. The main findings were as follows: (i) A decrease in the EP from ∼+75 to ∼+35 mV was produced by perilymphatic perfusion with CO₂/HCO₃⁻-free solution, which decrease was accompanied by an increase in the endolymphatic pH (ΔpH_e, ∼0.4). (ii) Perilymphatic perfusion with a solution containing 20 mM NH₄Cl produced a decrease in the EP (ΔEP, ∼20 mV) with an increase in the pH_e (ΔpH_e, ∼0.2), whereas switching the perfusion solution from the NH₄Cl solution to a 5% CO₂/25 mM HCO₃⁻ solution produced a gradual increase in the EP to the control level with the concomitant recovery of the pH_e. (iii) The perfusion with a solution of high or low HCO₃⁻ with a constant CO₂ level within 10 min produced no significant changes in the EP. (iv) Perfusion of the perilymph with 10 \\xb5 g/ml nifedipine suppressed the transient asphyxia-induced decrease in EP slightly, but not significantly. (v) By contrast, the administration of 1 μg/ml nifedipine via the endolymph inhibited significantly the reduction in the EP induced by transient asphyxia or perilymphatic perfusion with CO₂/HCO₃⁻-free or 20 mM NH₄Cl solution. These findings suggest that the effect of CO₂ removal from perilymphatic perfusion solution on the EP may be mediated by an increase in cytosolic Ca²⁺ concentration induced by an elevation of cytosolic pH in endolymphatic surface cells.

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This study used measures of heart rate variability during recovery from high-intensity exercise in trained Master athletes to examine postexercise cardiac autonomic regulation. Seven males (mean age 52.1 ± 3.3 yr; mass 85.1 ± 18.0 kg) and 6 females (mean age 50.5 ± 2.9 yr; mass 63.1 ± 6.0 kg) performed incremental exercise to an intensity that induced a >4.5 mmol capillary blood lactate concentration, followed by incremental exercise to volitional exhaustion (VO_2max). A 6 min ECG recording before (Pre) and after (Post) exercise was analyzed in the time (mean rr interval, sd rr) and frequency domains (total power, very low frequency [VLF: 0–0.04 Hz], low frequency [LF: 0.04–0.15 Hz], high frequency [HF: 0.15–0.4 Hz]). VO_2max for males and females was 49.4 ± 7.1 ml kg⁻¹ min⁻¹ and 45.1 ± 10.1 ml kg⁻¹ min⁻¹, respectively. Lower mean rr interval (Pre: 1,048 ± 128 ms; Post: 730 ± 78 ms; P < 0.001) and lower sd rr (Pre: 77 ± 30 ms; Post: 43 ± 17 ms; P < 0.001) were recorded following exercise, with no differences based on gender. Total power decreased following exercise (Pre: 6,331 ± 6,119 ms; Post: 1,921 ± 1,552 ms). When normalized for changes in total power, a decreased HF component (Pre: 34.52 ± 14.79 n.u.; Post: 18.49 ± 13.64 n.u.; P < 0.05) with no change in LF component (Pre: 61.00 ± 18.66 n.u.; Post: 69.63 ± 23.97 n.u.; P = 0.34) was recorded. No gender differences in HRV in the frequency domain were recorded. Decreased heart rate variability in both time and frequency domains suggested an increased parasympathetic withdrawal during the autonomic control of postexercise tachycardia in trained Master athletes.

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ACh-induced membrane responses in vascular endothelial cells that have been reported vary between preparations from a sustained hyperpolarization to a transient hyperpolarization followed by a depolarization; the reason for this variation is unknown. Using the perforated whole-cell clamp technique, we investigated ACh-induced membrane currents in freshly isolated endothelial layers having a resting membrane potential of less negative than −10 mV. A group of cells was electrically isolated using a wide-bore micropipette, and their membrane potential was well controlled. ACh activated K⁺ and Cl⁻ currents simultaneously. The K⁺ current was blocked by a combination of charybdotoxin and apamin and appears to result from the opening of IK_Ca and SK_Ca channels. The Cl⁻ current was partially blocked by tamoxifen, niflumic acid, or DIDS and appears to be produced by Ca²⁺-activated Cl⁻ channels. When the pipettes contained 20 mM Cl⁻, the ACh-induced K⁺ conductance started decreasing during a 1-min application of ACh while the Cl⁻ conductance continued, making the ACh-induced hyperpolarization sustained. When the pipettes contained 150 mM Cl⁻, both conductances started decreasing during a 1-min application of ACh, making the ACh-induced hyperpolarization small and transient. [Cl⁻]_i is very likely modified by experimental procedures such as the cell isolation and the intracellular dialysis with the pipette solution. Such a variability in [Cl⁻]_i may be one of the reasons for the variations in the ACh-induced membrane response.

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Although erythrocyte filterability plays a key role in microcirculation, it is unknown whether the filterability of erythrocytes from patients with chronic hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte filterability in CH-C patients in relation to medical treatment. The mean erythrocyte filterability (%) for all 24 patients with CH-C (69.2 ± 10.8%) was significantly lower than that for 5 normal controls (80.5 ± 1.7%, P < 0.03). In 8 patients, the combination therapy of ribavirin (RBV) and interferon improved liver function but caused anemia. The filterability after treatment (57.8 ± 12.8%) was lower than that before treatment (70.8 ± 9.7%, P < 0.05). Decreased filterability showed no correlation with the mean corpuscular volume or mean corpuscular Hb concentration during treatment, suggesting that the decrease in filterability mainly arises from changes in erythrocyte membrane properties. We investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV-induced anemia. Filterability in 7 responders was markedly improved from 68.4 ± 4.6% to 77.4 ± 2.4% (P < 0.001), but not in 3 nonresponders. In the responders, the progression of anemia was restrained. In conclusion, we found an obvious impairment of the filterability of erythrocytes from CH-C patients, further impairment of the filterability induced by oxidative membrane damage caused by RBV leading to hemolytic anemia, and amelioration of the filterability caused by the antioxidative effects of EPA.

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The follicular cells surrounding Xenopus oocyte under voltage clamp produce K⁺-current responses to follicle-stimulating hormone (FSH), adenosine (Ade), and intracellularly applied cAMP. We previously reported that these responses are suppressed by the stimulation of P2Y receptor through phosphorylation by PKC presumably of the ATP-sensitive K⁺ (K_ATP) channel. This channel comprises sulfonylurea receptors (SURs) and K⁺ ionophores (Kirs) having differential sensitivities to K⁺ channel openers (KCOs) depending on the SURs. To characterize the K⁺ channels involved in the FSH- and Ade-induced responses, we investigated the effects of various KCOs and SUR blockers on the agonist-induced responses. The applications of PCO400, cromakalim (Cro), and pinacidil, but not diazoxide, produced K⁺-current responses similar to the FSH- and Ade-induced responses in the magnitude order of PCO400 > Cro >> pinacidil in favor of SUR2A. The application of glibenclamide, phentolamine, and tolbutamide suppressed all the K⁺-current responses to FSH, Ade, cAMP, and KCOs. Furthermore, both the FSH- and Ade-induced responses were markedly augmented during the KCO-induced responses, or vice versa. The I–V curves for the K⁺-current responses induced by Cro, Ade, and FSH showed outward rectification in normal [K⁺]_o, but weak inward rectification in 122 mM [K⁺]_o. Also, stimulations of P2Y receptor by UTP or PKC by PDBu markedly depressed the K⁺-current response to KCOs in favor of Kir6.1, as previously observed with the responses to FSH and Ade. These results suggest that the K⁺-current responses to FSH and Ade may be produced by the opening of a novel type of K_ATP channel comprising SUR2A and Kir6.1.

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Aim: To analyze the correlation of the Poincaré plot descriptors of RR intervals with standard measures of heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS). A physiological model of changing respiratory rates from 6 to 15 breaths/min provided a wide range of RR intervals for analysis. Material and methods: Beat-to-beat finger blood pressure, ECG, and respiratory curves were recorded noninvasively in 15 young healthy volunteers (19–25 years old; 7 females) breathing for 5 min at 4 different respiratory rates of 6, 9, 12, and 15 breaths/min. Four descriptors of the Poincaré plot (SD1, SD2, S, and SD2/SD1), time and frequency domain HRV, and spontaneous BRS (cross-correlation method) were calculated for each 5-min recording. Results: The values of SD1 characterizing short-term HRV, SD2 describing long-term HRV, and S measuring total HRV were significantly correlated with BRS and time and frequency domain measures of short, long, and total HRV. The LF/HF significantly correlated with SD2 and SD2/SD1 representing the balance between long- and short-term HRV. None of the Poincaré plot descriptors was correlated with the mean RR interval. The increased respiratory rate caused a significant reduction of BRS, measures of total and long-term HRV, and an increase of HF that peaked at 12 breaths/min. Conclusions: The descriptors of the Poincaré plot of RR intervals are significantly correlated with measures of BRS and time and frequency domain HRV, but not with heart rate. A faster respiratory rate reduces long-term HRV measures and temporarily increases HF.

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The cardiovascular and ventilatory responses of the Wistar rat (a nonhibernator) and the Syrian hamster (a hibernator) to acute and chronic cold exposure were investigated. The acute lowering of core temperature (T_c = 22°C, hypothermia) compared with normothermia (T_c = 37°C) and hyperthermia (T_c = 40°C) was used to examine the underlying differences in the extent of cold adaptation. In euthermic rats, acutely induced hypothermia resulted in a pronounced reduction in heart rate (f_H reduced by 55%; P < 0.01), a modest but significant elevation of mean arterial blood pressure (mABP increased by 16%; P < 0.05), and a marked reduction in respiratory frequency (f_R reduced by 64%; P < 0.01). All parameters returned to baseline values on returning T_c to 37°C, with a modest overshoot on acute hyperthermia. These data are consistent with the depressive effect of low temperature on biological rate functions and increased vagal tone in the cold, while matching f_R to a lowered metabolic rate (MO₂). Cold acclimation had little effect on this pattern of response, suggesting that any adaptive increase in thermogenesis is limited. Euthermic hamsters also showed a significant reduction in f_H on acute cooling (74%; P < 0.01). In contrast to rats, hamsters developed a significant decrease in mABP (52%; P < 0.01) and maintained a relatively high f_R (4%; n.s.). These data suggest a resetting of the baroreflex and relative hyperventilation, consistent with an elevated MO₂ associated with enhanced nonshivering thermogenesis. Cold acclimation had little effect on thermal sensitivity, though the response curves were displaced to produce a relative hypertension and tachycardia at a given T_c. These data suggest a reduced cardiorespiratory coupling in the hibernator compared with the nonhibernator.

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The influence of hyperoxia on the cutaneous vasodilator responses to iontophoretic applications of acetylcholine (ACh) and sodium nitroprusside (SNP) was examined in healthy subjects. The breathing of 100% O₂ decreased (P < 0.05) the vasodilator response to Ach, but not to SNP, suggesting that hyperoxia attenuates endothelial-mediated vasodilation of the human skin.

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