Since the discovery of thermosensitive neurons in the POAH, numerous papers have been published suggesting the primary importance of these neurons in thermoregulation. The basic properties of the neurons per se were well studied in cultured explants and slice preparations, outside of the influences of anesthesia and extrahypothalamic inputs. Attempts have been made to classify thermosensitive neurons according to firing rate and response pattern and to correlate each neuron group with thermoregulatory responses. In complex thermoregulatory networks, thermosensitive neurons are always under the influences of extrahypothalamic and non-thermal inputs. Most studies on POAH neurons have shown a variety of responses, some contrary to others; for instance, three-fourths of POAH warm-sensitive neurons may be facilitated by scrotal warming whereas the rest are inhibited or uninfluenced. These inconsistencies in responses among thermosensitive neurons, observed also in the effects of chemicals, may reflect different roles of POAH thermosensitive neurons in a variety of thermoregulatory responses. Unit recordings from conscious animals over long periods, together with observation on whole body responses, are expected to throw more light on the physiological significance of POAH thermosensitive neurons.

View full abstract

We investigated the response of renal nerve activity (RNA) to hypercapnia and assessed the contribution of the peripheral chemoreceptors to the response of RNA in anesthetized and artificially ventilated cats. RNA and arterial pressure were recorded at four levels of PET_CO2, with hyperoxia in intact and in peripheral chemoreceptor denervated cats. In intact cats, RNA increased progressively with increasing PET_CO2, while no consistent change in arterial pressure was observed. In peripheral chemoreceptor denervated cats, the response of RNA to increasing PET_CO2 was totally abolished. These results suggest that the peripheral chemoreceptors play an important role in increasing RNA during hypercapnia.

View full abstract

An attempt was made to elucidate the site of action of grayanotoxin (GTX) in the nerve membrane by using various endopeptidases. The experiment was conducted on squid axons isolated from Doryteuthis bleekeli with both voltage clamp and internal perfusion methods. Intracellular application of various endopeptidases for more than 30min eliminated the gating action from both Na current and K current systems. When GTX (100μM) was subsequently applied to the internal medium, the membranes could depolarize to various extents. This finding strongly suggests that the site of action of GTX is not confined to the channel gating but is present in a part of the Na channel having both voltage sensor and ion filter functions. With the application of trypsin, St. fradiae trypsin, pronase, BPN′, and St. fradiae protease (group B), GTX-induced depolarization was much smaller than that with the application of α-chymotrypsin, N-protease, and thermolysin (group A). The difference in the sensitivity to GTX between group A and group B became remarkable as the time for application of the enzymes was prolonged. Since all enzymes belonging to group B retain trypsin-like activity and are more effective in removing the sensitivity to GTX, it is suggested that the molecular moiety around the binding site of GTX is rich in basic amino acids or the essential part for opening the Na channel should be protected by basic amino acids.

View full abstract

Cardiovascular response in an alerted state induced by vibration was studied in conscious rats by giving a to-and-fro movement to their cages for 30sec. Cardiac output, superior mesenteric flow, and hindquarter flow were observed with chronically implanted electromagnetic flow probes and arterial pressure with an indwelling catheter. Arterial pressure, heart rate, cardiac output and hindquarter flow increased and superior mesenteric flow decreased with vibration. The increase in heart rate was still present after adrenalectomy, but was abolished by β-adrenoceptor blockade propranolol. The increase in hindquarter flow was greatly diminished by propranolol or after adrenalectomy, but was still present in adrenalectomized rats after α-adrenoceptor blockade phentolamine. The decrease in superior mesenteric flow in vibration was abolished by phentolamine. It was diminished by adrenalectomy. These findings indicate that the cardiovascular response to vibration includes excitation of the cardiac sympathetic nerves, adrenomedullary secretion, and excitation of sympathetic vasoconstrictor fibers and exercise hyperemia in skeletal muscles.

View full abstract

1) Wistar rats were successively reared in cold at 5°C from 1969 to 1984. The historical changes observed in these rats were reported. 2) The cold-adapted rats reared in cold for 8 to 11 successive generations (C8-11G) were examined on their cold tolerance and nonshivering thermogenesis. C8-11G rats showed greater nonshivering thermogenesis than that of the warm-adapted control group (W), and rats exposed to cold for periods of 2 to 8 weeks (C). The nonshivering thermogenesis of C8-11G rats was diminished to a similar level to that of W and C rats by administration of a ganglion blocker, of reserpine, or of β-adrenoceptor blocker. 3) The de-adapted rats reared in warm at 25°C for 3 generations after being reared for many generations in cold (DA-3G) showed much more nonshivering thermogenesis as compared to W rats. Cold tolerance of DA-3G rats was at a level of intermediate between that of W and C rats. 4) Brown adipose tissue (BAT) weight of DA-3G rats was similar to that of C rats, while chemical composition of BAT in DA-3G rats differed from that of C and W rats.

View full abstract

The effect of i.v. infused ursodeoxycholate (1.2μmol/(min• 100g body weight)) was compared in control rats and in taurine supplemented (i.p. administration of a taurine solution) and taurine deprived (oral administration of β-alanine) rats. In the control rats, the bile water output during the first hr was significantly lower than that of the second hr, while the bile salt output was significantly lower in the second hr. In β-alanine pretreated rats, the increase in the bile flow in the first hr was more rapid compared to control rats, and the bile flow ratereached a peak earlier. The first hr and total 2hr bile water outputs were significantly higher in the β-alanine pretreated rats compared to the corresponding bile flow values of the control rats, while the bile salt outputs were significantly lower than respective control values. In taurine supplemented rats, the increase in bile flow in the second hr was less than in control rats, while the bile salt excretion rate was the highest among the three rat groups. Thus, among these three groups, the bile flow and bile salt excretion rate during the first hr and 2hr total infusion periods were negatively correlated. On the other hand, a significant positive correlation was observed between the bile flow rate for 1 or 2hr and bile salt concentration in the liver examined after a 1 or 2hr bile salt infusion. These results seem most easily explained by our previous thesis that at least part of the bile is produced not by the excretion of bile salt into the bile canaliculus but by its presence inside the hepatocyte (secretory mechanism).

View full abstract

Effects of aconitine and veratridine on membrane currents in the crayfish giant axon were studied under voltage-clamped conditions. Aconitine at 50μM reduced the Na current without changing the K current. The Na current left after aconitine block showed the activation and inactivation kinetics unaltered from the normal. These aconitineeffects differ from those reported previously with myelinated nerves. The rate of Na channel block by aconitine was increased with increasing either frequency or voltage of depolarizing pulses delivered repetitively from the holding potential but was not affected by a change in the pulseduration from 2 to 10msec. The same change in the pulse duration, however, caused about a 4-fold increase in the blocking rate in the axon of which inactivation process had been removed by a pretreatment with a sea anemone toxin from Parasicyonis actinostoloides. These results are explained by a model in which Na channels are occluded with aconitine molecules only when the channels are open. Veratridine at 50μM also exhibited frequency-dependent actions, depressing the maximum peak inward current and shifting the reversal potential of the transient current in the hyperpolarized direction. These veratridine effects persisted after washing. In addition to such persistent actions, veratridin induced a maintained Na current at the holding potential during repetitive stimulation. This effect was abolished after a brief wash unlike the above-mentioned persistent effects, suggesting that veratridine has two (or more) different modes of actions on Na channels in the crayfish giant axon.

View full abstract

Using isolated bullfrog retina treated with both aspartate and Ba²⁺, the relation between the threshold of fast PIII response and rhodopsin content was examined. The change caused by a decrease in rhodopsin in response threshold from the original dark-adapted level could be described by the Michaelis-Menten equation. However, the data points deviated slightly from the theoretical curve when the rhodopsin content was below 30%. After reducing Ca²⁺ concentration in the bathing solution from the normal (1.0mM) to 0.01mM, the threshold change of the response was more pronounced than that observed in the normal solution. In the presence of 0.1mM papaverine, which is known as an inhibitor of phosphodiesterase, the threshold change increased in a similar way to that observed in 0.01mM Ca²⁺ solution. However, isobutyl methylxanthine (IBMX), also an inhibitor of phosphodiesterase, showed no such effect. On the basis of the present findings, the transduction mechanism in the photorecep ors was discussed.

View full abstract

Relationships between the change in threshold of the fast PIII response and the rhodopsin photoproduct content were studied in the isolated bullfrog retina treated with Ba²⁺ and aspartate. A reduction in the extracellular Ca²⁺ concentration from 1.0 to 0.01mM caused an increase in the decay rate of 380nm absorbing photoproducts (metarhodopsin II and retinal) and metarhodopsin III. In both normaland low Ca²⁺ solutions, the threshold change after bleaching of about 50% of rhodopsin was closely related to the 380nm absorbing photoproducts. The results suggest that the intermediate adaptation process of rods may be regulated by the 380nm absorbing photoproducts.

View full abstract

The changes of venous outflow (Q_v), hematocrit (Hct), total plasma protein (T_p), electrolytes, crystalloid osmolality, P_O2, P_CO2, and pH were simultaneously measured in hindlimb preparation of anesthetized rabbits during 5min occlusion of the femoral artery and the abdominal aorta and during the reactive hyperemia. During the occlusion of the femoral artery, Q_v decreased to 66.4% at the end of the occlusion. Hct and T_p decreased slightly and then tended to progressively increase. P_O2 showed an increasing trend following an initial decrease. During the occlusion of the aorta, Q_O2 showed a continuous drop to 38.0%, while Hct and T_p declined to 95.4 and 93.8%, respectively. Q_v, Hct, and T_p showed increase after the release of the occlusion of the femoral artery and the aort . Crystalloid osmolality and K⁺ were observed to rise slightly. From these results it was suggested (1) that the increase of Hct and T_p which represents the hemoconcentration occurred during the reactive hyperemia and during the occlusion of the femoral artery, while the hemodilution occurred during the aortic occlusion, and (2) that the gradual increase of Hct and T_p during the occlusion of the femoral artery would be caused by the collateral blood flow.

View full abstract

The present study was designed to determine effect of the preganglionic splanchnic nerve activity (SNA) on the brief hypotension accompanied with the occlusion of left circumflex coronary artery (CxCAO) in chloralose anesthetized cats. Following CxCAO in animals with neuraxis intact, no significant alterations of SNA occurred despite the significant fall in mean blood pressure (MBP). A significant fall in MBP also occurred in vagotomized animals with arterial baroreceptors intact, but SNA was significantly augmented from 12.9±2.7impulses/sec before CxCAO to 24.4±4.3impulses/sec 60sec after the occlusion. In vagotomized animals, in which their carotid sinuses were isolated and perfused with the constant pressure at a level equal to systemic blood pressure (112±6mmHg) and with higher pressure (167±7mmHg), SNA was not altered significantly during the hypotension due to CxCAO. When the carotid sinuses were perfused with lower pressure (53±8mmHg), a significant increase in SNAoccurred simultaneously with the decrease in MBP after CxCAO. The peak decreases in blood pressure during the coronary occlusion were significantly greater in the vagotomized group (-46±5mmHg) and in the Low-CSP group (-50±5mmHg) than in other groups. Onset of this excitatory efferent sympathetic response to the hypotension due to the coronary occlusion in the vagotomized and Low-CSP groups was delayed significantly despite a significant fall in arterial blood pressure. These results show that vagal afferents from the heart may play a role of inhibiting the sympathetic augmentation mediated by arterial baroreceptors during cardiogenic hypotension. An excessive activation of cardiac receptors with sympathetic afferents may be induced by the profound fall in blood pressure, resulting in further impairment of cardiac function due to progressive myocardial ischemia under the condition of high sympathetic tone activated by baroreceptor reflex.

View full abstract

The differentiation of the sodium active transport system across Rana catesbeiana skin during metamorphosis was investigated and the system was analyzed by the effects of Cd²⁺ and amiloride. Active transport of Na in the frog skin first appeared at stage XXI of the tadpole, indicated by the appearance of a potential difference (PD) and a short circuit current (SCC) across the skin. The effects of epidermal application of Cd²⁺ and amiloride on the various indicators of active Na transport were as follows: (1) Cd²⁺ increased PD and SCC after stage XXII; (2) Cd²⁺ also increased the skin resistance (R_M) from stage B to XXIII, but decreased it after stage XXV; and (3) amiloride decreased PD and SCC but increased R_M after stage XXI. The adult frog skin can be expressed as an equivalent circuit by three parameters: E_Na, the electromotive force of the active Na current, and R_Na and R_Σ, corresponding to the resistance to the active Na current and the resistance of the shunt pathway, respectively. These three parameters were calculated from the amiloride effect on PD and SCC. E_Na was almost null and R_Na was infinite until stage XX. E_Na then gradually increased, while R_Na was fairly constant between 10 and 20KΩ•cm² after stage XXI. R_Σ gradually increased during metamorphosis. These data suggest that there is not an active Na pathway but a passive one in the early stage of metamorphosis of the tadpole, and that the active Na transport system suddenly appears at stage XXI and gradually develops thereafter.

View full abstract