The experimental results on the hemodynamics and mechanisms of the systemic arterial pressure oscillation (SAPO) produced by the side pressure exertion procedure (SPEP) are presented.
The SAPO has revealed us the existence of reciprocal structure at the base of the nervous integration of the cardiovascular system. The reciprocity is found between the type I and type II vasomotor neurons in the bulbar cardiovascular center. The latter is in charge of making the hierarchical set-up in the cardiovascular system, in which blood is supplied to the brain and the cardiac muscle at the expense of blood supply to the other organs. The former is in charge of building antihierarchical set-up, in which blood is provided to the other organs including the cardiac muscle at the sacrifice of blood supply to the brain. During the SAPO, the two groups of the reticular vasomotor neurons alternately discharge, and the two set-ups appear by turns in the cardiovascular system. Thus the animal can survive the SPEP for hours.
The SAPO is caused by the coupling of the existing reciprocity with a newly generated central oscillator. The central oscillator has a segmental structure. It is composed of unit oscillators combined in series. This structure works as a ruler of the powerful CNS ischemic response and endows the SAPO with both rigidity and plasticity. It has shown the exsistence of segmental organization in the CNS in the chronological aspect also and the role of the CNS as that more than mere reflex centers. The study on the SAPO has opened a way to the physiology on emergence of a new order in the animal body.

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Synergistic effects of Ca²⁺ -mediated secretagogues and cyclic AMP-mediated secretagogues on Cl^- secretion by guinea pig distal colon were studied in vitro using Ussing chambers. Short-circuit current (I_sc) and bidirectional fluxes of ²²Na⁺ and ³⁶Cl^- were measured. Bethanechol (10^-4M, a Ca²⁺-mediated secretagogue) caused an increase in I_sc, which was enhanced 4-20 fold when the tissue was pretreated with prostaglandin E₂ (10^-7-10^-6M), vasoactive intestinal polypeptide (5×10^-9-10^-8M) (cyclic AMP-mediated secretagogues), or 8-bromocyclic AMP (5×10^-4-2×10^-3M). Measurement of ³⁶Cl flux showed that the increase in I_sc in the presence of both 8-bromocyclic AMP and bethanechol resulted principally from increased Cl^- secretion. On the other hand, the net absorptive flux of ²²Na was not influenced under these conditions. Potentiation of the increase in I_sc was also elicited by the combination of A23187 (5×10^-6M) and 8-bromocyclic AMP (10^-3M). The results are consistent with the notion that simultaneous activation of the cyclic AMP-mediated and Ca²⁺-mediated systems produces a synergistic increase in colonic Cl^- secretion.

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To estimate the influence of ventilatory conditions on the CO₂ equilibration between the alveolar gas and arterial blood during steady state hypercapnia, we measured arterial and end-tidal P_CO2 (Pa_CO2, PET_CO2) of the anesthetized rat under the following three conditions: spontaneously breathing with CO₂ inhalation, artificial respiration with gas mixture containing CO₂, and artificial respiration with reduced ventilatory volume (hypoventilation). In each ventilatory condition, Pa_CO2 correlated linearly with PET_CO2. However, in spontaneously breathing animals, the Pa_CO2-PET_CO2 difference which was positive in a control condition (without CO₂ inhalation) became negative during CO₂ inhalation. The mean (±S.D.) difference was -3.6±1.5mmHg (n=9, p<0.001) at the PET_CO2 range from 72 to 77mmHg. During artificial respiration with constant ventilatory volume, initial positive Pa_CO2-PET_CO2 difference approached zero when CO₂ was administered into inspiratory gas. In both ventilatory conditions the slope of the PET_CO2-PaCO₂ relation line was less than 1.0, whereas the PaCO₂-PET_CO2 difference remained positive when P_CO2 level was increased with reducing the ventilatory volume (accumulation of endogenous CO₂). These observations suggest that for a given increase in P_CO2 by administration of exogenous CO₂, the extent to which PaCO₂ increases is smaller than that of PET_CO2. This peculiar relationship together with changes in breathing pattern during CO₂ inhalation likely results in "negative" PaCO₂-PET_CO2 difference in the spontaneously breathing animal. We conclude that the PaCO₂-PET_CO2 difference, either as positive or negative values, depends upon both the level of P_CO2 and the ventilatory condition to increase P_CO2.

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We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl₄ (2mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0±38.7mmH₂O) than in the control normal Wistar rats (NWR) (102.0±25.5mmH₂O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K⁺, Ca²⁺, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]_o (5.4-86.4mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]_o (0.45-5.4mM), under conditions of 86.4mM [K]_o was significantly larger in PHR than in NWR preparations. However, the Ca²⁺ sensitivity of both preparations was the same. D-600 (≥0.1μM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10μM), the Ca²⁺ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the α₁-adrenoceptor blocker, prazosin (0.1μM). The α₁-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca²⁺ release and uptake of intracellular Ca²⁺ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca²⁺ permeability. The PHR preparations have a higher affinity for external Ca²⁺ in the presence of norepinephrine, an additional factor contributing to elevation of portal blood pressure in the presence of chronic liver cirrhosis.

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On assumptions that tympanic temperature (T_ty) reflects brain temperature and that the latter can be lowered by cooling of the face, effect of facial cooling during acclimation process on adaptive changes in sweating activity was examined, in comparison with the results of our previous studies on heat acclimation with controlled hyperthermia. Face fanning, by which T_ty was clamped at approximately 37.1°C, was combined with either of the following 9-day acclimation procedures: 90-min heating in a "Sauna box, " keeping mean skin temperature slightly above 40°C, or 90-min exercise on a bicycle, clamping rectal temperature (T_re) at approximately 38°C. Each procedure was imposed on the same four male subjects on different occasions, two of whom had participated in our previous experiments. Sweat tests, carried out before and immediately after the completion of the procedure, consisted of measurements of local sweat rates, whole body sweat rate, T_re, T_ty and skin temperatures on 5 areas, and of calculations of mean body temperature (T_b) and the rate of sweat expulsions (F_sw, as an indicator of central sudomotor activity). No or only a slight increase in sweating activity was observed following the acclimation procedures with face fanning, whereas similar procedures without face fanning had resulted in substantial enhancement of sweating activity in most of the cases, which had been attributed mainly to adaptive changes in central sudomotor activity (as indicated by a shift of the regression line relating F_sw to T_b). Similar results were obtained in an additional series of experiments, where the effects of 9-day 90-min exercise in heat, clamping T_re at approximately 38.2°C, with and without facial cooling, were compared with each other in a subject. From the above results it is inferred that T_ty reflects brain temperature and that enhancement of sweating activity induced by repeated heat load is strongly impeded, if not accompanied, by an elevation of brain temperature.

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The effects of baroceptor reflex on mean cardiac (MCSNA) and renal sympathetic nerve activity (MRNA) were analyzed before and after atropinized (0.1mg/kg, i.v.) states in conscious cats at rest. Resting values of MCSNA, MRNA, mean aortic pressure (MAP), and heart rate (HR) were 85±6imps/s, 76±11imps/s, 100±4mmHg, and 164±10beats/min, respectively. Both MCSNA and MRNA changed almost inversely to changes in the absolute MAP in the range of 90-140mmHg. Within this pressure range the gain of baroceptor-sympathetic system to the heart and kidney was 2.31 and 1.84, respectively. MCSNA as well as MRNA was reduced to the noise level at the MAP of 142 and 150mmHg, respectively. With atropine, MCSNA and MRNA were inhibited centrally whereas HR increased to 192beats/min. The increase in MAP caused by norepinephrine (2.1μg/kg, i.v.) was enhanced to 75±7mmHg by atropine from 31±4mmHg in control. The piecewise linear MAP-MCSNA and MAP-MRNA relationships changed to a remarkable clockwise hysteresis loop. During the rising MAP period, the gain of the baroceptor-sympathetic system decreased to 0.91 and 0.97 in MCSNA and MRNA, respectively. During the returning MAP period, a delayed activation in MCSNA and MRNA occurred centrally. We conclude that the baroceptor reflex effect on MCSNA is larger than those on MRNA, and that the baroceptor control of MCSNA and MRNA is modified centrally by atropine in the awake cat at rest.

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With a computerized impedance cardiograph we measured stroke volume (sv), cardiac output and heart rate (HR) in four men, during apnea with positive or negative intrapulmonic pressure (i.e., Valsalva and Mueller maneuver) in air. During Valsalva maneuvers the sv was reduced, and the compensatory rise in HR failed to keep the cardiac output at the control level before apnea. During both types of apnea, the diastolic pressure was increased as was the total peripheral resistance (TPR). The vasoconstriction and tachycardia during Valsalva maneuvers can be explained as a sino-aortic baroreceptor phenomenon in man. The smaller changes occurring during Mueller maneuvers result in no change in the transmural arterial pressure in the thorax, compared to the control level. Thus, without a stimulus there is no change in heart rate. The alveolar oxygen uptake and carbon dioxide elimination during apnea at total lung capacity was much larger than in the control phase before both types of apnea. The arteriolar vasoconstriction with increased TPR during the Valsalva apnea, was accompanied by a reduction in the stroke work of the left ventricle to approximately 50% of the work in the control phase.

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Seven rats were exposed to a hot environment (36°C) for about 5h to induce thermal dehydration. They were allowed to recover from their fluid loss; both tap water and 1.8% NaCl solution were provided simultaneously as drinking fluids. In the recovery stage, these animals initially consumed low NaCl solution (about 41mEq/l) for the first 90min and then shifted to drinking slightly hypotonic NaCl solution (about 122mEq/l) on the average. To analyze the mechanism driving the above shift, changes in blood volume (BV), plasma Na concentration ([Na]), and the amount of water and 1.8% NaCl solution consumed were measured continuously. After 4h of recovery, BV increased by + 1.1ml/100g body wt. and reached 5.7ml/100g body wt. (set as 100%) while plasma [Na] reduced by -5.5mEq/l or to 141.5mEq/l (mean values of 7 rats). The shift of [Na] of drinking water was observed when plasma [Na] reduced to -3.4mEq/l or 62.3% of the 4th-hour level, while BV recovery remained only +0.5ml or 46.3%. A response to urinary output started later when plasma [Na] reached 142.6mEq/l or 83.1%, while BV recovery remained +5.4ml or 76%. These results indicate that the regulation of plasma [Na] takes precedence over the regulation of BV. This conclusion is in agreement with the view that the blood osmolality change directly modifies the cell volume whereas circulatory function under decreased blood volume can be regulated by change of the vascular compliance.

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The effects of cholinergic and adrenergic agonists on intercellular communication in isolated acini of rat submandibular gland were evaluated using dye-coupling. Cells injected with Lucifer Yellow CH showed diffusion of the dye to their coupled neighbors under the control condition. Addition of acetylcholine (ACh) and carbachol (CCh) at concentrations higher than 10^-6M rapidly and reversibly suppressed the dye-coupling. This effect by 10^-4M ACh or 10^-4M CCh was blocked by the addition of 10^-6M atropine. The suppressive effects of 10^-4M adrenaline and 10^-4M noradrenaline were weaker than those of 10^-4M ACh. Treatment with 10^-4M isoproterenol did not inhibit the dye-coupling and the suppressive effect by 10^-4M adrenaline was blocked by the addition of 10^-5M phenoxybenzamine. The inhibition of dye-coupling by ACh and adrenaline was blocked by the addition of 10^-5M verapamil, 10^-4M W-7 and 1.5×10^-5M H-7, but not by 1.5×10^-5M HA1004. These results suggest that the muscarinic action of cholinergic agonists and the α-action of adrenergic agonists might suppress the intercellular communication of the acinar cells in the rat submandibular gland, possibly through the increase of calcium influx and the activation of protein kinase C.

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Hindquarter peripheral resistance, calculated as arterial pressure divided by hindquarter blood flow, decreased significantly on ganglionic blockade with hexamethonium bromide in four kinds of experimentally hypertensive rats, i.e. spontaneously hypertensive rats (SHR), DOCA-salt hypertensive rats, and one-kidney, one-clip and two-kidney, one-clip renovascular hypertensive rats, but not in normotensive control rats in the conscious state. Abnormal hindquarter vasoconstrictor tone seems to be a feature common to various kinds of hypertensive rats.

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A transient urinary acidification was induced in the bullfrog proximal tubule by the peritubular administration of ouabain (10^-4M). Insulin (200mIU/ml) provoked a prolonged decrease of tubular fluid pH (TF_pH), whereas dibutyryl cyclic AMP (10^-4M) produced a transient increase of TF_pH. The above data support the view that the urinary acidification in the proximal tubule is not explained by a simple mechanism, such as Na⁺/H⁺ exchange.

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Day-by-day changes in ventricular-ejection time/heart-rate ratio (VET/HR) and in ejection time index (ETI), determined by an impedance method in a decompression chamber, were more labile in the mountaineers who had experienced high altitude (above 6, 000m) within the past 1 year, and the ETI values in the first hypoxic exposure were significantly high in these subjects, though close to those of the non-experienced group in the later exposures, suggesting that the effect of hypoxic acclimation on cardiac function might remain at least 1 year after return to sea level.

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Acetylcholine (ACh) induces a hyperpolarization during current clamp and an outward current during voltage clamp in tail sensory neurons of Aplysia kurodai. This response was proved to be produced by a specific increase in membrane permeability toward potassium ions. the cholinergic antagonists, d-tubocurarine chloride (d-TC), and atropine mildly reduced the ACh response, while tetraethylammonium (TEA) most effectively blocked this response. These findings provide evidence that tail sensory neurons have the inhibitory ACh receptor in addition to the known receptors for serotonin (5-HT), small cardioactive peptide_B (SCP_B), and neuropeptide Phe-Met-Arg-Phe-NH₂ (FMRFamide).

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The corticotectal pathway from the fundus of the cat's coronal sulcus (CORo) from which monocular movements of contralateral eye were evoked was studied using electrophysiological and anatomical techniques. Neurons in the CORo were activated antidromically by electrical stimulation of the deep layer of the superior colliculus (SC). Labeled cells were found in the CORo following horseradish peroxidase injection in the SC.

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A new method for determining the nonlinear characteristics of pneumotachometers was developed. This method consists of a computer algorithm analyzing unsteady flows generated by a syringe. We removed the possible influence of the frequency characteristics of the measuring system by inserting an acoustic low pass filter in the path of gas flow. Two types of Fleisch pneumotachometers were tested. For a given volume of 3l, the error of measured volume is 12.5% in uncorrected series and 0.2% in the corrected.

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Morulae were collected from rabbit vaginas after prostaglandin treatment 65h post coitum. The optimum embryo recovery was obtained when the flushings started around 12h after the prostaglandin injection. The mean embryo collection was around 10 embryos per animal. These embryos had the same viability as those collected by the classical technique of uterine flushing (around 80%). The freezing ability of these embryos was also similar to that observed for uterus-collected embryos. Embryos not ejected after the treatment can develop in vivo and give birth to living progeny. The results obtained suggest that this technique can be used for egg transfer in rabbit genetic improvement programs.

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