Mammalian skeletal muscle fibers are classified into three basic types based on their enzyme histochemical profiles: fast-twitch glycolytic (FG), fast-twitch oxidative glycolytic (FOG), and slow-twitch oxidative (SO) types. The type-shift of fibers from FOG to SO in the slow soleus muscle of rats occurs during postnatal growth. Our previous studies have demonstrated that hypoxic exposure inhibits a growth-related type-shift of fibers from FOG to SO in the rat soleus muscle, irrespective of the duration and age at which the animals are exposed to hypoxia. Our previous studies have also revealed that a high percentage of FOG fibers in the soleus muscle of the hypoxia-adapted rats is found only under hypoxic conditions. Furthermore, we have found that these adaptations in fibers of the rat soleus muscle correspond well with those in motoneurons at the ventral horn of the spinal cord that innervate the muscle fibers.

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The molecular behavior of water in normal and regenerating tendons was analyzed using the transverse relaxation time (T₂) measured by spin-echo proton nuclear magnetic resonance (¹H-NMR) spectroscopy at 2.34 T (25°C). A section of the Achilles tendon was dissected from an anesthetized Japanese white rabbit, and its longitudinal axis was oriented at 0, 35, 54.7, 75, and 90° to the static magnetic field. In the normal tendon, the T₂ relaxation of water presented biexponential relaxation and anisotropy in both the long T₂ (5.41 to 6.21 ms) and short T₂ (0.41 to 1.43 ms) components, in which the greatest values were obtained at 54.7°. However, the range of the anisotropy was much narrower than we expected from the ¹H dipolar interaction of water bound to the collagen fibers in the tendon. The apparent fractions of water proton density also varied with orientation: the fraction of the longer T₂ components was at its maximum at 54.7°. These results suggest that a simple two-compartment model could not be applicable to orientational dependency of the T₂ value of the tendon, and the well ordered water in the short T₂ relaxation component may show an elongated T₂ relaxation time that falls in the range of the long T₂ relaxation component at 54.7°. This hypothesis can explain both the narrower range of the T₂ relaxation time and the orientational dependency on the apparent fraction of ¹H density. Regenerating processes of the Achilles tendon were followed for 18 weeks by analyzing the T₂ relaxation time. There is only a long T₂ relaxation time component (21.8 to 28.0 ms) up to 3 weeks after transection. Biexponential relaxation is revealed at 6 weeks and thereafter, whereby (i) the T₂ relaxation times become shorter, (ii) there is anisotropy in the short and long T₂ values, and (iii) the orientational dependency of the apparent fraction of water proton density becomes evident with maturation of the regenerating tendon. From these results, the ¹H T₂ relaxation time of water might be used to monitor the healing process of collagen structures of the tendon non-invasively.

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Little information is available regarding the influence of the intensity of endurance training over biochemical profiles in cardiac muscle. We assessed the effect of running training at two different intensities on cardiac myosin isozyme composition in rats. Male Sprague-Dawley rats (4 weeks old) were divided into four groups: sedentary control (SC), trained at 20 m/min (T20), trained at 40 m/min (T40), and weight-matched sedentary control (WMSC) groups. The T20 and T40 group rats were trained by treadmill running for 60 min/d, 5 d/week at 20 or 40 m/min, respectively, for 11 to 12 weeks. In both groups the left ventricle was significantly heavier than in WMSC animals. The ratio of left ventricle weight to body weight was significantly greater in T40 rats than in either the untrained (SC and WMSC) or trained T20 rats. Thus the extent of exercise-induced cardiac hypertrophy appears to be influenced by the intensity of running training. However, neither of the training programs (1) induced a change in cardiac myosin isozyme composition or (2) had any effect on myocardial succinate dehydrogenase or citrate synthase activity. These results suggest that although the intensity of running training may play an important role in cardiac morphological adaptation, it does not modulate the cardiac biochemical adaptation to running training.

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A cholinergic neural vasodilative response in the cerebral cortex and hippocampus, independent of metabolic vasodilation, was recently demonstrated by activating the nicotinic acetylcholine receptors (nAChRs) via activation of cholinergic neurons originating in the nucleus basalis of Meynert and septal complex in the basal forebrain and projecting to the cortex and hippocampus (see reviews by Sato A and Sato Y: Neurosci Res 14: 242-274, 1992; Sato A and Sato Y: Alzheimer Dis Assoc Disord 9: 28-38, 1995). In the present study, we aimed to examine whether an increase in regional blood flow in the hippocampus (Hpc-BF) following stimulation of the nAChRs by i.v. injection of nicotine could improve the delayed death of the hippocampal neurons following transient ischemia in rats. Hpc-BF was measured by using a laser Doppler flowmeter. During intermittent (every 2 min) transient occlusion for a total of 6 min of bilateral carotid arteries besides permanent ligation of bilateral vertebral arteries, Hpc-BF decreased to about 16% of the preocclusion level, and 5 or 7 d later, after the occlusion, delayed neuronal death occurred in approximately 70% of the CA1 hippocampal neurons. Hpc-BF was increased dose-dependently by injection of nicotine (30-100 μg/kg, i.v.), independent of mean arterial pressure. Nicotine (30-100 μg/kg) administered 5 min before occlusion slightly but significantly attenuated the occlusion-induced decrease in Hpc-BF. The delayed death of the CA1 hippocampal neurons occurring after transient occlusion was attenuated by pretreatment with nicotine (30-100 μg/kg) to approximately 50% of the total neurons. The results indicate that nAChR stimulation-induced increases in Hpc-BF can protect against ischemia-induced delayed death of hippocampal neurons.

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In the guinea-pig renal pelvis, most smooth muscle cells examined (>90%), using a conventional microelectrode, had a resting membrane potential of about −50 mV and produced spontaneous action potentials with initial fast spikes and following plateau potentials. The remainder (<10%) had a resting membrane potential of about −40 mV and produced periodical depolarization with slow rising and falling phases. Experiments were carried out to investigate the properties of spontaneous action potentials. The potentials were abolished by nifedipine, suggesting a possible contribution of voltage-gated Ca²⁺ channels to the generation of these potentials. Niflumic acid and 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), inhibitors of Ca²⁺-activated Cl⁻ channels, showed different effects on the spontaneous action potentials, and the former but not the latter inhibited the activities, raised the question of an involvement of Cl⁻ channels in the generation of these activities. Depleting internal Ca²⁺ stores directly with caffeine or indirectly by inhibiting Ca²⁺-ATPase at the internal membrane with cyclopiazonic acid (CPA) prevented the generation of spontaneous activity. Chelating intracellular Ca²⁺ by 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA) increased the amplitude of the spike component of spontaneous activity. Indomethacin inhibited the spontaneous activity, whereas prostaglandin F_2α enhanced it. The results indicate that in smooth muscle of the renal pelvis, the generation of spontaneous activity is causally related to the activation of voltage-gated Ca²⁺ channels through which the influx of Ca²⁺ may trigger the release of Ca²⁺ from the internal stores to activate a set of ion channels at the membrane. Endogenous prostaglandins may be involved in the initiation of spontaneous activity.

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We have previously shown that the inhibitory respiratory response, which we call post-stimulus suppression, is induced by nociceptive muscular afferents. This phenomenon is thought to be caused by a negative feedback induced by excessive afferent inputs. In the present study, we investigated whether augmented levels of prestimulus respiration would influence the magnitude of poststimulus suppression by recording the phrenic nerve discharges in chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated cats. The respiratory level was augmented by means of either hypercapnia, hypoxia or naloxone administration, all of which markedly facilitated the peak amplitude (PK) of integrated phrenic discharges, neural tidal volume. When the electrical stimulation of thin-fiber muscular afferents was performed at these augmented PK levels, the magnitude of poststimulus suppression in the PK was markedly attenuated without consistently altering the facilitatory response during the stimulation period. It seems that the facilitatory component of the augmented level of resting respiration may reduce the inhibitory component of poststimulus suppression. The results indicate that prestimulus respiratory activity is an important factor in determining the magnitude of poststimulus suppression.

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Noxious stimulation of thin-fiber muscular afferents induces a reflexive respiratory suppression that we call "poststimulus respiratory suppression." In anesthetized, vagotomized, paralyzed, and artificially ventilated cats, morphine depressed the level of resting respiration (inhibitory effect on resting respiration) and attenuated the magnitude of the poststimulus respiratory suppression (excitatory effect on the reflexively modified respiration). These two kinds of morphine effects were antagonized by naloxone, suggesting the participation of opioid receptors. To clarify the opioid receptor subtypes responsible for these effects of morphine, three type-selective opioid antagonists—naltrindole (δ antagonist), β-funaltrexamine (μ antagonist), and Mr2266 (κ antagonist)—were tested. The morphine-induced depression in the resting respiration was antagonized by pretreatment with the κ antagonist, not with the μ or δ antagonist. Furthermore, the morphine-induced attenuation in the magnitude of the poststimulus suppression was also blocked by the κ antagonist, but not by the μ or δ antagonist. In conclusion, (1) morphine inhibits resting respiration, but it attenuates the magnitude of the poststimulus respiratory suppression; (2) both these morphine effects are mediated by κ opioid receptors. The possibility that the κ₃ receptor, one of the κ receptors subtypes, mediates the two kinds of morphine effects has been discussed.

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The effects of membrane depolarization on the frequency of spontaneous activities were investigated in circular smooth muscle of the guinea-pig antrum attached with (intact tissue) or without longitudinal muscles (circular tissue). Both types of tissue were spontaneously active; the intact tissues generated slow wave and circular tissues generated regenerative potential. The latter but not the former was abolished by caffeine. Increasing K⁺ concentrations depolarized the membrane and reduced the amplitude and interval between spontaneous activities in both tissues; the amplitude was reduced linearly with depolarization and disappeared at about −35 mV; the interval was reduced successively with depolarization and reached a stable value (about 8 s) at about −45 mV. The depolarization and reduction in amplitude and interval of spontaneous activities induced by high K⁺ solution were not altered by atropine, nitroarginine, or apamin in either tissue, suggesting that these changes did not involve the effects of neurotransmitters. The depolarization of the membrane by electrical stimulation also reduced the amplitude and interval of spontaneous activities in both tissues, in a potential-dependent way. The absolute refractory period for generation of the evoked regenerative potential was about 8 s, and the relative refractory period was 8-12 s. The results indicate that the frequency of slow waves increases with a depolarization of the membrane up to −45 mV, irrespective of the presence of caffeine-insensitive components. A depolarization of the membrane above −45 mV does not further increase the frequency of slow waves, possibly because of the refractory period for the generation of slow waves.

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The ion channel conductances that regulate the membrane potential was investigated by using a perforated patch-clamp technique in rabbit aorta endothelial cells (RAECs). The whole-cell current/voltage (I-V) relation showed a slight outward rectification under physiological ionic conditions. The resting membrane potential was −23.3 ± 1.1 mV (mean ± SEM, n = 19). The slope conductances at the potentials of −80 and 50 mV were 31.0 ± 4.0 and 62.8 ± 7.1 pS pF⁻¹, respectively (n = 15). Changes in the extracellular and intracellular Cl⁻ concentrations did not affect the reversal potential on I-V curves. The background nonselective cationic (NSC) current was isolated after the K⁺ current was suppressed. The relative permeabilities calculated from the changes in reversal potentials using the constant-field theory were P_K:P_Cs:P_Na:P_Li = 1:0.87:0.40:0.27 and P_Cs:P_Ca = 1:0.21. Increases in the external Ca²⁺ decreased the background NSC current in a dose-dependent manner. The concentration for half block by Ca²⁺ was 1.1 ± 0.3 mM (n = 7). Through the continuous recording of the membrane potential in a current-clamp mode, it was found that the background NSC conductance is the major determinant of resting membrane potential. Taken together, it could be concluded that the background NSC channels function as the major determinant for the resting membrane potential and can be responsible for the background Ca²⁺ entry pathway in freshly isolated RAECs.

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In this study, we demonstrated that PKC inhibitors significantly attenuated the cardioprotective effect produced by high-glucose (22 mM) treatment for 48 h against hypoxic injury in H9c2 cardiac cells. PKC activators mimicked the cardioprotective effect of high glucose. These results suggest a possible role of PKC activation in high-glucose-induced protection.

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We examined the effects of progesterone on the elevation of tail skin temperature (TST) in ovariectomized rats and compared them with those of estradiol. Progesterone showed only insignificant effects on the TST elevation, whereas estradiol showed complete inhibition. The TST elevation induced by ovariectomy is caused by estradiol deficiency, but progesterone plays little or no role.

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