Nerve fibers produce several non-electrical signals on excitation. Recent findings on such non-electrical signals are discussed, in the hope that some of them might give us clues to molecular events underlying the excitation process. At present this expectation is not fulfilled, but progress is being made which allows one to look optimistically at future developments.

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The effect of airway anaesthesia by nebulization of 4% lidocaine was studied in 14 healthy human subjects. After airway anaesthesia, a small but significant increase in forced vital capacity and a decrease in expiratory peak flow rate were observed in the pulmonary function test. Blood gas analysis revealed the appreciable depression in arterial oxygen tension. This change was accompanied by the increased alveoler/arterial oxygen tension difference (p<0.01) and increased oxygen uptake (p<0.01). Resting respiratory rate increased. Although minute ventilation was not changed, mouth occlution pressure (P_0.2) was significantly elevated. Hypercapnic ventilatory responses were augmented, both in terms of VE/PET_CO2 and P_0.2/PET_CO2 slopes. The load compensation ratio, expressed as P_0.2 loaded/P_0.2 unloaded at rest, was reduced. These results suggested that preferential blockade of vagally mediated pulmonary stretch receptors by airway anaesthesia rather than the irritant receptors may have resulted in augmentation in ventilatory activities.

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A rebreathing method was developed to obtain the pulmonary diffusing capacity for CO, DL(CO) and the cardiac output, Q, simultaneously at rest and during exercise. From DL(CO) and Q, contact time of the red blood cell (RBC) through the lung capillary, t_c, was estimated by referring to a reaction rate factor of CO with RBC, F_c(CO). The DL(CO) and Q were calculated from the changes in CO, O₂, and CO₂ concentrations in rebreathing air. The F_c(CO) was evaluated so as to attain a proportional relation between the DL(CO) and F_c(CO) by varying a transfer coefficient for CO across the RBC boundary including the capillary wall. The P_O2 dependence of Q was also taken into account in the above analyses. The t_c was determined by dividing the DL(CO) by F_c(CO), Q, and fractional hematocrit. The DL(CO) and _Q measured in five normal subjects in a sitting position were 26.6±2.9ml•min^-1•Torr^-1 and 5.9±0.6l•min^-1 (mean±S.D.), respectively, which increased during moderate exercise up to 34.6±3.9ml•min^-1•Torr^-1 and 13.0±1.2 l•min^-1. The t_c, was 0.70±0.06s at rest and 0.40±0.05s during exercise. The rebreathing method for measuring DL(CO) was more advantageous than the single breath method, because (1) the t_c could be obtained as well as the Q and (2) the influence of the dead space and ventilation-perfusion uneveness on DL(CO) was reduced.

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Cortical collecting ducts (CCD) and inner stripe of outer medullary collecting ducts (OMCD) of the rabbit were perfused in vitro and the electrical potential was measured with 0.5M KCl-filled conventional microelectrodes. In CCD, the transepithelial potential (V^te) was -1.9±0.5 (S.E.) mV and the intracellular potential (V^b) was -74.5± 1.3mV, while in OMCD, V^te was +2.0±0.4mV and V^b was -24.6± 1.0mV. Acute reduction of peritubular HCO₃^- concentration from 25 to 5mM (from pH 7.4 to 6.9) decreased V^b slowly but markedly from -26.3±1.8 to -18.9±1.6mV (p<0.001) in OMCD, while it depolarized V^b slightly in CCD (from -75.6±1.9 to -74.3±2.1mV, p<0.05). Acute peritubular pH reduction with HCO₃^--free HEPES-buffered solution also depolarized V^b of OMCD from -24.7±2.1 to -15.9± 1.6mV (p<0.001). Although the mechanism(s) of V^b depolarization in OMCD is unclear at the moment, this depolarization suggests that OMCD is responsive to peritubular pH alterations. The results of this study provide the evidence that the collecting duct is heterogeneous in V^b values and its response to the peritubular pH change.

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The responses of neurons in the arcuate nucleus (ARC) to γ-aminobutyric acid (GABA), glycine, serotonin (5-HT), norepinephrine (NE), and dopamine (DA) were examined in hypothalamic slices from ovariectomized rats either treated or untreated with estrogen. In estrogen-untreated preparations, spontaneous unit activity of the majority of neurons identified antidromically by the median eminence (ME) stimulation was depressed by GABA and glycine. When effective, 5-HT was predominantly excitatory and DA was predominantly inhibitory, while NE evoked both excitatory and inhibitory responses. The IS-SD block in evoked spikes was also occasionally observed following GABA and glycine perfusion. The responsiveness of unidentified neurons, which were not activated by the ME stimulation, to agents other than 5-HT did not differ from that of antidromically identified neurons. Responses of unidentified neurons to 5-HT were predominantly inhibitory. Subcutaneous injection of 20μg of 17β-estradiol-benzoate 2 days prior to the experiments did not significantly affect the responsiveness of both identified and unidentified neurons to GABA, 5-HT, DA, and NE. Contrarily, preincubation of slices in 17β-estradiol-containing medium (10nM) for 1h significantly increased the responsiveness of unidentified, but not identified, neurons to the inhibitory action of NE. These results suggest that GABA, glycine, 5-HT, NE, and DA play some functional roles in controlling the excitability of tuberoinfundibular (TI) neurons in the ARC. It is also suggested that the negative feedback effect of estrogen is mediated, at least in part, by increased responsiveness of ARC neurons other than TI neurons to the inhibitory action of NE.

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Cholinergic modulation and effects of dynorphin on the nonadrenergic non-cholinergic inhibitory potentials (NANC i.p.s) in the longitudinal smooth muscle cells of the guinea-pig duodenum were studied intracellularly. Atropine (1.4×10^-7-1.4×10^-5M) and scopolamine (3.3×10^-8-3.3×10^-7M) increased the amplitude of the evoked i.p.s while physostigmine (3.7×10^-7-3.7×10^-6M) and neostigmine (4.8×10^-8M) decreased it. The frequency of the spontaneous action potentials in the longitudinal smooth muscle cells was increased by dynorphin (6×10^-8-3×10^-7M) without continuous membrane depolarization. The excitatory effect of dynorphin on the spontaneous electrical activity was not blocked by atropine (1.4×10^-6M). Dynorphin (6×10-8- 2.4×10^-7M) increased the amplitude of the i.p.s evoked in the presence of atropine (1.4×10^-7-1.4×10^-6M) and in the propranolol (3.9×10^-6M) solution containing atropine while dynorphin decreased the amplitude of the i.p.s evoked in the absence of atropine. In the high calcium solution containing atropine, the amplitude of the i.p.s increased. Further increase in the amplitude of the i.p.s was observed by additively applied dynorphin. However, the amplitude of the i.p.s evoked in the high calcium solution without atropine was decreased by dynorphin. These results suggest the cholinergic inhibitory modulation on the NANC inhibitory nerves in the guinea-pig duodenum, the non-cholinergic excitatory action of dynorphin on the spontaneous electrical activity of the, longitudinal smooth muscle and the excitatory action of dynorphin on the NANC inhibitory nerves in the presence of muscarinic blocking agents.

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Under pentobarbitone anesthesia, arterial blood pressure and heart rate were recorded in rabbits. The elevation in systemic blood pressure and increased heart rate induced by electrical stimulation of the right thoracic sympathetic nerve trunk were depressed by either an intravenous injection of diltiazem (300μg/kg) or by placing cotton pledgets soaked in 2mM diltiazem solution onto the right stellate ganglion. These inhibiting effects of diltiazem were statistically significant with high sympathetic stimulation frequencies (10-20Hz), but not when lower frequencies (1-5Hz) were used. On the other hand, hexamethonium (10mg/kg i.v. or 100mM applied topically) depressed cardiovascular responses to sympathetic stimulation over a wide range of frequencies (1-20Hz). Present results reveal a frequency-dependent inhibition of ganglionic transmission by diltiazem, and suggest that diltiazem may depress excessive sympathetic activity without affecting normal ganglionic transmission.

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Centrum medianum (CM) afferent pathways, which are involved in pain sensation, were analyzed using physiological techniques. Thirty-four neurons in the gigantocellular nucleus (nucleus gigantocellu- laris medullae oblongatae, GC) in cats were recorded intracellularly. Of these, 5 (15%) did not respond to electrical stimulation applied to any of the 4 limbs. Twenty-nine (85%) showed spike potentials that were superimposed on excitatory post-synaptic potentials (EPSPs) with an amplitude of 7.2mV (n=101) and a duration of 6.8ms. The latencies from contra- and ipsilateral forelimb, contra- and ipsilateral hindlimb to the GC were 9.3 (n=25), 7.2 (n=23), 12.9 (n=28), and 10.9ms (n=25), respectively. Of these responding neurons, 19 (66%) responded to stimuli to all 4 limbs, 7 (24%) to 3 limbs, 1 (3%) to 2 limbs, and 2 (7%) to 1 limb. These afferent neurons in the GC showed spike potentials without EPSPS after stimulation of the CM in the thalamus. Extracellular activities of 37 CM neurons were also tested. Of these, 4 neurons responded to GC stimulation with a short latency of 1.6ms. Another 33 responded with a long latency of 6.7, and 11 of them were able to follow GC stimulation of over 200Hz with a fixed long latency; 22 responded with varying long latencies but were not able to follow stimuli over 15Hz. Three-quarters of the CM neurons received ipsilateral inputs from the GC, and the other contralateral inputs. Three CM neurons responded to stimulation of the GC in quasi-intracellular records. These findings suggest that some ascending fibers from the GC terminate on CM neurons and play a role in pain sensation.

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Quantitative analysis of myoglobin (Mb) was established using the sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis in order to determine the influence of thermal acclimation on Mb levels in muscles. Myoglobin was measured in the red and white parts of quadriceps, soleus, diaphragm and heart of young adult male rats (11 weeks old). It was higher in the red muscle (0.92±0.043mg/g fresh weight) than in the white muscle (0.08±0.007), and similar in the red muscle and soleus (1.17±0.117). Heart showed the highest level (1.52±0.073) among the tissues studied. The level in diaphragm (0.74±0.039) was intermediate between red muscle and heart. Cold acclimation (5°C for 4 weeks, 11 weeks old) caused significant increases in Mb levels in white muscle (0.27±0.031, p<0.001), heart (1.95±0.094, p<0.01), and diaphragm (1.01±0.060, p<0.01), but not in red muscle and soleus. The rats reared in cold for many generations (20 generations at 5°C, 11 weeks old) manifested significant increases in Mb levels of all tissues (p<0.05-0.001) examined. Heat acclimation (33°C for 4 weeks, 11 weeks old) did not influence Mb levels of the tissues. The above findings suggest that skeletal muscle Mb may be partly involved in an enhanced thermogenesis in cold acclimation by favouring an oxidative capacity of muscles.

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Quick stretches applied to the helical strips of rabbit cerebral artery produced marked delayed tension development. The stretch-induced contraction was more resistant to the removal of [Ca²⁺]_o and Ca antagonists than the mechanical response to high [K⁺]_o and electrical stimulation, and was absent in chemically skinned preparations, indicating that it is not an inherent property of the contractile mechanism per se. The effect of the removal of [Ca²⁺]_o and drugs such as dantrolene and ryanodine. indicated that the intracellular origin of Ca²⁺ was involved in the stretch-induced contraction. To explore the above possibility, the intracellular Ca localization in rabbit cerebral artery smooth muscle was examined by the pyroantimonate method. In muscle cells fixed at rest, the pyroantimonate precipitate containing Ca was localized along the inner surface of the plasma membrane, while in muscle cells fixed during the stretch-induced contraction the precipitate was diffusely distributed in the myoplasm. These results strongly suggest that the stretch-induced mechanical response is associated with the Ca²⁺ release from the inner surface of the plasma membrane.

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Ability to utilize urea nitrogen for body protein synthesis was examined with Papua New Guinea (PNG) highlanders and Japanese (JPN). Eight male PNG highlanders and 8 male JPN were fed on a low protein diet containing 0.55g protein/kg or an adequate protein diet containing 1.34g protein/kg for 1 or 2 weeks. The fate of ¹⁵N was measured after oral administration of ¹⁵N-labelled urea. There was no difference in ¹⁵N incorporation into serum protein between PNG highlanders and JPN receiving low protein diets. On the other hand, on the adequate protein diet, ¹⁵N incorporation in PNG highlanders was similar to that on the low protein diet, in contrast to that in JPN which was hardly detected in the adequate protein diet. When PNG highlanders take more protein than protein in their usual diet, they effectively incorporate ingested protein into their body protein and urea nitrogen is utilized for synthesis of body protein.

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Length and conduction velocity were determined in muscle fibers belonging to the single motor unit (right m. vastus medialis) in the living human body. A new method was developed for measuring the length of fibers, i.e., the muscle length was defined to be the distance between the starting point of excitation (motor end-plate) and the distal end of muscle fibers belonging to the particular motor unit. Both points were decided by analyzing the shape of the spike potentials of the motor unit recorded by surface electrodes. The length increased by about 70% (ranging from 48% to 97%) when changing the knee angle from fully extended to the fully flexed position, whereas the conduction velocity decreased by about 26% (ranging from 17 to 36%). It can be considered that the decrease of the conduction velocity when increasing the length of the muscle fibers was mainly due to the decrease in fiber diameter.

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The mechanism of spontaneous contraction of vascular smooth muscles in the elastic artery was studied in a ring-shaped preparation isolated from the rat aorta. The observation of small changes in vascular tension with a high gain AC amplification of tension signal provided a reliable detection of spontaneous contractions. The spontaneous rhythmic contraction (RC) occurred consistently in the preparation taken from the thoracic aorta without external stimuli. The RC (frequency, 5-20 cycle/min; amplitude, 10-100mg) was accompanied with small oscillatory changes in the membrane potential (2-5mV, peak to peak). A reduction in temperature (below 30°C) or superfusing the preparation with Ca-free solution inhibited the generation of RC. Ca-entry blockers (verapamil and nifedipine) also inhibited the RC. The cessation of RC by these procedures reduced the vascular tension by about 40% of control baseline tension. The application of adrenergic blockers had little effect on the pattern of RC and on the vascular tension. The results suggest that the RC is generated by a synchronization of electrical and mechanical activities in relatively small groups of smooth muscle cells, which depends upon the temperature and requires the Ca-entry into the cells. The process of initiation of spontaneous RC in the rat aorta was discussed.

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Noradrenaline (NA), but not clonidine applied microiontophoretically, inhibited the firing of neurons in the rat Al noradrenergic region, whereas intravenous clonidine dose-dependently inhibited their firing (ED₅₀=18.3μg/kg). The NA-induced inhibition was blocked by the β-antagonist timolol, but not by the α-antagonists phentolamine or piperoxane. These results suggest that neurons in the Al region possess β- adrenoceptors rather than α-adrenoceptors near their cell bodies, and that systemically administered clonidine acts indirectly on these cells.

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Rat mast cells treated with Ca-free medium were stimulated with Ca reintroduction and its secretory mechanism was investigated. The response was modulated by experimental manipulations which are supposed to alter the level of internal Na, suggesting the involvement of internal Na in this response.

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Two groups of SHR were treated with captopril (Squibb): the first group (1 month old)-30mg/kg i.p. twice daily for 77 days, and the second group (8 months old)-20mg/kg p.o. twice a day for 23 days. The recording of electrocardiogram (ECG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and some isometric indices of the left ventricular contractility indicate that in all treated animals the values of most of the parameters are considerably lowered compared to the controls. The ratio between velocity of pressure increase and intraventricular pressure/equal to 50mmHg-(dP/dt)/ICP₅₀/does not change significantly It can be concluded that in SHR, captopril practically does not influence the inotropic condition of the myocardium.

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Metyrapone caused significant increase of V_O2 in cold-acclimated rats, but not in warm controls and heat-acclimated rats. Plasma FFA decreased, while plasma glycerol increased in all groups. Glycerol increase was less in heat-acclimated rats than in other groups. FFA/glycerol molar ratio decreased most in cold-acclimated rats.

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