129

J. Physiol. (1978), 274, pp. 129-139 With 4 text-figurea Printed in Great Britain

HEPATIC PORTAL VEIN INFUSION OF GLUCOSE AND SODIUM SOLUTIONS ON THE CONTROL OF SALINE DRINKING IN THE RAT

BY WILLIAM D. BLAKE AND K. K. LIN From the Department of Physiology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, U.S.A.

(Received 15 March 1977) SUMMARY

1. Rats were prepared under anaesthesia with non-occlusive catheters in hepatic portal vein (HP) and inferior vena cava (VC) and maintained under standard conditions. 2. Each rat received a series (3 day intervals) of 30 min infusions of different solutions or sham into HP or VC. Oral intake of 0 15 M-NaCl and water were measured for 30 min. Significant change in drinking behaviour was assumed when the response to HP infusion differed from both sham and VC infusion. 3. Saline drinking was inhibited by HP infusion of 1 M- or 2 m-NaCl, an effect blocked by right vagotomy or by addition of 16 mM-KCl to the infusate. 4. Saline drinking was increased and water drinking decreased by HP infusion of 2 M-glucose but not sucrose or fructose. 5. Saline drinking was decreased by HP infusion of deoxy-D-glucose to inhibit glucose utilization or ouabain to inhibit (Na+-K+) ATPase. 6. Results are consistent with the presence of afferent nerve terminals in hepatic portal vessels which are sensitive to change in NaCl or glucose concentration and which, in response thereto, alter drinking behaviour. The effects of NaCl and glucose on the discharge rate of the nerve terminals may be interpreted in terms of changing activity or electrogenicity of a Na pump but changes in membrane conductance or Na influx cannot be ruled out. INTRODUCTION

Despite some reports to the contrary (Potkay & Gilmore, 1970; Schneider, Davis, Robb, Baumber, Johnson & Wright, 1970) electrophysiological (Niijima, 1969a; Andrews & Orbach, 1973, 1974; Adachi, Niijima & Jacobs, 1976) and behavioural (Daly, Roe & Horrocks, 1967; Strandhoy & Williamson, 1970; Lin & Blake, 1971; Passo, Thornborough & Rothballer, 1973) studies provide good evidence for neural receptors located in the liver which are sensitive to increased sodium concentration in the blood of the hepatic portal vein. There is conflicting evidence with respect to gluco-sensitive receptors (Niijima, 1939b; Andrews & Orbach, 1973; Russek, 1970; Stephens & Baldwin, 1974) and osmoreceptors (Schneider et al. 1970; Niijima, 1969a; Andrews & Orbach, 1974; Adachi et al. 1976; Passo et al. 1973; PHY 274

W. D. BLAKE AND K. K. LIN 130 Haberich, 1968). The present report deals with the sodium and glucose receptors involved in the control of NaCl solution drinking and with some of these characteristics which are consistent with dependence on an electrogenic Na pump. METHODS Experiments were conducted on five groups of rats, some groups being arbitrarily subdivided for some experiments since it was not deemed essential to do all infusions on all rats of a group. The number of rats in each group and the treatments are shown with the results. The details of the experimental procedures have been published (Lin & Blake, 1971). Male Sprague-Dawley rats, 350-425 g, were individually housed and offered rat chow, water, and 0-15 m-saline solution ad lib. Under anaesthesia PE-10 tubing was implanted in a mesenteric vein leading into the hepatic portal vein (HP) and also in the inferior vena cava (VC). The catheters were passed under the skin to the top of the head where they were available for attaching to tubing from an infusion pump. Following recovery (a week) rats were infused with 0-5 ml. solution over a 30 min period into either HP or VC or not at all (sham infusion). The volume of solution and time of infusion were selected after preliminary trials which were done to define a minimum volume over time which gave unequivocal results. In two groups of rats (I and V) sham and NaCl infusions were done before and after right-sided cervical vagotomy carried out under anaesthesia with pentobarbitone, 40 mg/kg body wt. intraperitoneally. Individual test runs were at least 3 days apart, randomized for site of infusion or sham and solution infused, and were highly standardized to minimize irrelevant variables. The rat was deprived of fluids for 24 hr and brought to the laboratory in his home cage. One of the catheters was attached to the pump, or sham attachment, and the pump was turned on. After 15 min of infusion the rat was offered water and 0 15 M-NaCl to drink, after 30 min the pump was turned off, and after 45 min (30 min drinking time) the volumes of water and saline solution ingested were measured. The 30 min drinking period was used since by this time most control animals had essentially completed the burst of drinking induced by 24 hr of withholding fluids. In addition, saline drinking preference was calculated as the saline drunk as per cent of total fluid drunk during the 30 min period. For some groups, fluid intakes were measured at the end of 24 hr (including the 30 min) but the time course of ingestion was not followed. Since all rats in a group or sub-group received all the infusions recorded for that group, analysis of results was by the method of paired comparisons. Hepatic portal vein infusions were considered to have a significant effect related to the portal circulation only when the means were consistently significantly different from those of both sham and VC infusions. RESULTS

The concentrations of the solutions infused are given with the Results and Figures. If the hepatic portal plasma flow was no more than 6 ml./min (Larsen, Krarup & Munck, 1976), considered more likely than the value used previously (Lin & Blake, 1971), then, with the infusion rates used, a 2 M solution would have increased hepatic portal plasma solute concentration by at least 5-6 mm above the control level, a 1 M solution by 2-8 mm, etc. The concentration of ouabain reaching the tissues would have been at least 1-9x 10-6 M, sufficient to partially inhibit neural (Na+-K+) ATPase in the rat (Ahmed & Judah, 1964). Hepatic portal vein (HP) infusion of 2 M- or 1 M-NaCl consistently decreased saline intake and preference compared either with sham or VC infusion of the same solution (Figs. 1-3). Saline preference is not shown in Fig. 1 but was decreased in control experiments. There were no consistent effects on water intake, intake after HP infusion never differing from sham and differing from VC infusion on only one occasion (1 M-NaCl, Fig. 2). After right-sided cervical vagotomy, HP infusion of

SALINE DRINKING CONTROL 131 2 M-NaCl failed to decrease saline drinking (Fig. 1) or saline preference (not illustrated). This block of the effect of HP NaCi was observed in other vagotomized rats receiving 4 M-NaCl (Group V, not illustrated, n = 14) but these experiments were considered less satisfactory because of possible side effects of 4 M solutions (Lin & Blake, 1971). Vagotomy per se had no consistent effect on water or saline drinking during the sham infusion period or during the 24 hr intake period. Saline drinking o Differs from S * Differs from VC A Differs from pre-vagotomy control

20 _

C~~~~~~ ~~~z

0

C

(n 15

-

LO,

2

E~

0S T

10

5

0 M

S

VC

HP

S

VC

HP

Control Right vagotomy 2 m2 mNaCI NaCI Fig. 1. Effect of right cervical vagotomy on saline and water drinking responses to sham (S), vena cava (VC), and hepatic portal (HP) infusion of 2 M-NaCl solution. Values are means ± s.E. of mean (vertical lines). Group I rats (n = 12) were used before and after vagotomy. Differences considered significant when P < 005 by method of paired comparisons.

(n)

(12)

was greater during sham in Group I (Fig. 1) but not in Group V and in only one sub-group (n = 8) of Group V was there any increase in saline intake over 24 hr. These results are essentially consistent with the negative results of Adachi et al. (1976). VC infusion of 2 M- or 1 M-NaCl solution decreased saline drinking compared with sham in Group II rats (Fig. 2) but not in Group I (Fig. 1) or Group III (Fig. 3) rats. Similarly inconsistent effects were seen with respect to water intake. These results will, therefore, not be considered further. HP infusion of 2 M-glucose consistently increased saline intake and preference and decreased water intake (Figs. 2 and 4). HP infusion of 1 M-glucose increased saline intake but failed to increase significantly saline preference or decrease water 5-2

132 W. D. BLAKE AND K. K. LIN intake (Fig. 2). Given by VC, neither 2 M- nor 1 M-glucose had any consistent effect on saline or water drinking (Fligs. 2 and 4). HP infusion of 0-3 M-glucose, 2 Mfructose, or 2 M-sucrose was without significant effect (Fig. 2). HP infusion of deoxyD-glucose (20 g/100 ml.), an inhibitor of glucose utilization (den Hertog, Greengard & Ritchie, 1969) significantly decreased (P < 0.05) saline intake but not preference when compared with either sham or VC infusion. Values (Group IIIB, n = 8, not * Differs from VC

Differs from S 1-1

I-

75

-i 0

Z I-,

50

0 c

*-~ 25 a

z I-

0

15

E

is

0

10 I-I')

+

z

0O

0

:,

.

I

LOl

-o

5

En

0

0 I

0

(n)

+ S

.

IVCIHPIVCIHPIVC m A

(13) 2

.f

M-

A

1

NaCI

M-

2

HP HP M-

glucose

+

±

+ S Ivc (6)

1

HP

VCIHP

M-

0*3

glucose

M-

s (7)

HAP

H 2 M-

fruct.

2 M-

sucr.

Fig. 2. Effect of infusing NaCl and various sugar solutions on saline and water drinking and saline preference. Group II rats (n = 13) were subdivided into sub-groups A (n = 6) and B (n = 7) for some experiments. Values are means with s.E. of mean given only for sham infusions since analyses were by paired comparisons. Differences were considered significant when P < 0-05.

illustrated) for saline intake were: sham infusion 5-5 + 1-4, VC infusion 3-9 + 0-9, and HP infusion 2-1 + 0-8 ml./30 min. Water intake decreased but only compared with sham infusion (sham 13-0 + 1-3, VC 6-8 + 0-8, HP 5-1 + 0-9 ml./30 min). VC infusion of deoxy-D-glucose did not significantly influence saline drinking but water intake was less than after sham infusion (see above). When 16 mm- or 32 mM-KCl was added to a 1 M-NaCl solution, HP infusion had no significant effect on saline drinking or preference compared with sham or VC infusion (Fig. 3), a contrast to the reduction seen with 1 M-NaCl alone. Water intake was not consistently altered. When 32 mM-KCl was added to isotonic (0.15 M) rather than the hypertonic (1 M) NaCl, VC infusion increased saline drinking and preference and decreased water intake compared to sham infusion (Fig. 3). Infusion

133 SALINE DRINKING CONTROL of the isotonic or 0415 M-NaCl by itself is without effect (Lin & Blake, 1971). In other words, KCl blocked the effect of HP infusion of 1 M-NaCl in reducing NaCl intake and, at sufficiently high concentration, increased saline intake when the liver was by-passed. The rats receiving the 32 mM-KCl appeared restless, exploring the cage, but displayed no other neurological signs of excitation or depression. HP infusion of 0 7 mM-ouabain or 20 mM-EDTA (Ca2+ chelating agent) depressed saline intake and preference compared sham or VC infusion (Fig. 4). Water intake 50

0

50

Differs from S Differs from VC

0) E !-> 25

0 20 0

~150 015 mNaCI (8

- C)

10

13

-

1M

!2

1

8

0

0

,as

C

NC

0

~~~0

c

U_

N

S VC HP VCHP S VC HP VCHP M1 m NaCI (8) 1 m 0.15 m 16 mm KCI 32 mm 32 mm

0.-.

(n) (n)

18)1 mmi (18)O

Fig. 3. Effect of adding KCl to infusions on saline and water drinking and saline preference. Group III rats (n= 18) were subdivided into subgroup A (n = 8) for some experiments. For further explanation see Fig. 2.

was also depressed but significantly only compared to sham infusion (Fig. 4). VC infusion of either drug also depressed saline intake but not to the same extent as HP infusion and had no significant effect on saline preference. The 24 hr fluid intakes are also shown for this group to indicate absence of any marked reductions in intake, presumably indicating lack of any persistent toxicity. If anything the tendency was for VC infusions to be more effective than HP. HP infusion of 2 mM-epinephrine or 2 mM-norepinephrine in 0 15 M-NaCl was without significant effect on saline or water intake (not illustrated). At the anticipated blood flow, the concentration of catecholamine in the hepatic portal blood should have been approximately 5 X 10-6 M.

W. D. BLAKE AND K. K. LIN

134

00 'J5J

C

60

0~~~~~~~~~~~~ C Z

~325

.~~~~~~~~~~50

Z 0

-7 o . 40

-

0 Differs from S Differs from VC 15 C T VC H P VC

E

000 015 22 M0Z?10 -NaCI

Co

0

3

Co 5 (N

~~~~~~~~200

S VC HP VCHP VCHP S VC HP VCHP VCHP 2 M- 0-7 mm- 20 mmmm0.7 mm20 (n) (18) 2 mglucose ouabain EDTA glucose ouabain EDTA Fig. 4. Effect of glucose, ouabain, and EDTA infusions on saline and water drinking (30 min and 24 hr) and on saline preference. Group IV rats (n = 18) were used in all infusions. For further explanation see Fig. 2. 0

DISCUSSION

From the results certain conclusions seem clear. Hepatic portal infusion of 1 Mor 2 m-NaCl inhibited saline drinking without consistently affecting water intake, thereby decreasing both saline intake and preference. The effect was mediated by neural receptors which transmitted the information to the central nervous system via the right vagus. HP infusion of 1 M- or 2 M-glucose stimulated saline drinking but only 2 M-glucose significantly decreased water intake and increased saline preference. Inhibition of glucose utilization with deoxy-D-glucose (den Hertog et al. 1969) decreased saline intake but not preference. However, deoxy-D-glucose infusion decreased water intake regardless of infusion site. Presumably, deoxy-D-glucose effects were not limited to hepatic afferent nerve terminals and this other effect could have obscured any effect on saline drinking preference. What then is the nature of the nerve terminals or receptors responding to NaCI and glucose? There is anatomical evidence for some specialized receptors in the liver but the majority of afferent fibres in the blood vessels are free endings (Tsai, 1958). Ample electrophysiological and functional evidence for neural receptors sensitive to NaCl exists (see Introduction). Most pertinently, vagotomy blocked the natriuretic response to HP infusion of hypertonic NaCl (Passo et al. 1973), and Niijima (1969a) and Adachi et at. (1976) found increased impulse activity in single afferent nerve fibres from isolated, perfused guinea-pig and rat livers when the perfusate concentration of NaCl was raised by as little as 5 mm. Andrews & Orbach (1974) observed

135 SALINE DRINKING CONTROL increased discharge rate by adding 8-5 mm-NaCl to the perfusate. Neither group found that the NaCl sensitive neurones were responsive to increased glucose concentration. In a separate report, Niijima (1969b) did note decreased impulse activity when the perfusate concentration of glucose was raised but this was presumably a separate group of fibres. Andrews & Orbach (1973) failed to confirm the glucose effect. Consequently, there is evidence to suggest that NaCl sensitive receptors are not responsive to glucose, at least in the isolated perfused liver. Some (Niijima, 1969a; Adachi et al., 1976; Haberich, 1968) maintain that the receptors are not specifically NaCl sensitive but respond to changes in osmotic pressure. Others find no evidence for osmoreceptors (Schneider et al. 1970; Andrews & Orbach, 1974; Passo et al. 1973; Lin & Blake, 1971). Current negative results with 2 m-fructose and 2 m-sucrose infusions also fail to implicate an hepatic portal osmoreceptor in the control of saline or water drinking. The preponderance of evidence suggests, that neither the responses to HP infusion of NaCl nor those to glucose are referable to osmoreceptor activation. If, as seems likely (Niijima, 1969a; Andrews & Orbach, 1973), these putative receptors are spontaneously discharging neurones, the rate of firing might be altered in a number of ways, e.g. a depolarizing effect due to Na influx or change in membrane permeability to Na or to inhibition of an electrogenic Na pump. With regard to postulated hypothalamic Na receptors, Denton (1966) and Mouw & Vander (1970) have discussed the possibility that changes in intracellular Na concentration might alter cell excitability. In their view, influx of Na would inhibit cell activity in the neurones stimulatory to sodium intake. Inhibition by ouabain of NaHCO3 drinking in Na-depleted sheep was considered consistent with this concept (Denton, Kraintz & Kraintz, 1970). It would be equally plausible to suggest that Na influx increased cell excitability in neurones inhibitory to sodium intake and more consistent with the results of Niijima (1969a) and Andrews & Orbach (1974) and with the excitatory action of ouabain on neurones or their terminals (Saum, Brown & Tuley, 1976; Sokolove & Cooke, 1971). There is no evidence relating to Na or glucose effects on membrane permeability within the range of concentration change used in these experiments. Livengood & Kusano (1972) and Saum et al. (1976) have discussed the possible role of an electrogenic Na pump in altering spontaneous firing. This latter possibility merits further discussion. The following argument, admittedly speculative, is presented in support of an electrogenic pump mechanism. Assume that the postulated Na (or Cl) sensitive receptors are small, unmyelinated nerve terminals metabolically dependent on glucose to supply energy for a (Na+-K+)ATPase-dependent, electrogenic Na pump (den Hertog et al. 1969; Kerkut & York, 1971). Further assume that the activity and/or electrogenicity of the pump determines a significant fraction of the receptor membrane potential. The spontaneous discharge rate of the receptors would be determined, at least in part, by the degree of hyperpolarization of the receptor membrane created by the electrogenic Na pump (Livengood & Kusano, 1972; Saum et at. 1976). Any inhibition of pump activity or decrease in electrogenicity would tend to depolarize the membrane and increase receptor discharge rate. The receptors are assumed to transmit inhibitory impulses to the central controller system for saline drinking. Given these assumptions, the results of the experiments may be

W. D. BLAKE AND K. K. LIN readily explained. Even small increases in Na concentration outside might suppress a Na-inside-stimulated pump, as external Na does in Na-loaded frog skeletal muscle (Sjodin, 1971). Alternatively, the increased Na outside might enhance Na for Na exchange (Kerkut & York, 1971; DeWeer, 1970) and decrease the electrogenicity of the pump. Either way discharge rate would be enhanced by a small increase in external Na concentration. Recently a decrease in baroreceptor discharge rate was found with a small (5 %) decrease in external Na concentration (Kunze, Saum & Brown, 1977), further confirming the effect of Na concentration on the discharge rate of mammalian nerve terminals. The stimulation of saline drinking by HP glucose infusion is presumed to result from decreased impulse activity (Niijima, 1969b) of the fibres inhibitory to saline drinking. Increased glucose substrate could provide additional ATP to further enhance pump activity; at least, the dependence of previously-stimulated electrogenic pump activity on glucose metabolism has been demonstrated both by removal of glucose and by inhibition of its utilization with deoxy-D-glucose (den Hertog. et al. 1969). Alternatively, increased glucose metabolism might elevate hepatic temperature and thereby increase pump activity (Kerkut & York, 1971). The inhibition of saline drinking by ouabain may be explained as the result of increased receptor discharge secondary to membrane depolarization by partial inhibition of the electrogenic Na pump. Neural ATPase is far more sensitive to inhibition by ouabain than is liver tissue ATPase (Ahmed & Judah, 1964) and the concentration reaching the neural receptors in the liver should have been sufficient to inhibit ATPase to some extent. Ouabain-induced increased firing rate in other neural systems has been recently demonstrated and also attributed to inhibition of an electrogenic Na pump (Livengood & Kusano, 1972; Saum et al. 1976). The inhibition of saline drinking by EDTA presumably resulted from receptor activation, perhaps mediated by pump inhibition or by depolarization of the membrane by increasing permeability to Na (Chambaut, Leray-Pecker, Feldman & Hanoune, 1974). The mechanism here is not clear. The action of KCl in blocking the action of NaCl could be twofold, i.e. both at the membrane of the receptor and at some other site as well, perhaps central. The evidence for both actions is good. Andrews & Orbach (1974) increased the discharge rate of hepatic afferent nerves by raising the Na (or Li) concentration out of proportion to the concentrations of the other electrolytes. However, they found no change in receptor discharge if Na and K concentrations were raised proportionately by adding less water to the perfusion mixture. Similarly, we found no inhibition of saline intake if 16 mM-KCl was added to the HP infusion of 1 M-NaCl. A stimulatory effect of slightly elevated external K on the Na pump could have hyperpolarized the receptor membrane (Marmor & Gorman, 1970) and suppressed spontaneous activity. In addition to this local effect, a central action of K is indicated by the studies in which saline drinking was increased when 32 mM-KCl in isotonic saline 136

Although this observation eliminates the necessity for effect at the hepatic receptor, it certainly does not preclude postulating any blocking such an effect. Infusion of KCl might also have stimulated secretion of aldosterone (Boyd & Mulrow, 1972) which enhances saline drinking when given in sizeable doses (Wolf, McGovern & DiCara, 1974). was infused into the VC.

137 SALINE DRINKING CONTROL In brief, the case for an hepatic neural receptor sensitive to physiological changes in Na (or Cl) concentration in hepatic portal vein blood has been presented. Given certain assumptions, the discharge rate of the receptor may be linked inversely to the activity and/or electrogenicity of the (Na+-K+)ATPase dependent pump in the receptor membrane. Against this conclusion is the finding of Andrews & Orbach (1974) that Li could partly substitute for Na to maintain spontaneous firing. One can only surmise that in vivo receptors and those in the isolated perfused liver may respond differently. This is apparently true with respect to glucose receptors. Note also the discrepancy in the results between Niijima's (1969b) studies and those of Andrews & Orbach (1973). Perhaps the weakest assumptions in the model are that the Na pump is sufficiently active and electrogenic to be instrumental in defining membrane potential (Rang & Ritchie, 1968) and that such small changes in external Na concentration could significantly alter pump activity or electrogenicity. However, electrogenic Na pump activity can partly define spontaneous (non-stimulated) firing rate in other systems (Livengood & Kusano, 1972; Saum et al. 1976), one of which is a mammalian neural receptor. Further, Niijima (1969a) and Andrews & Orbach (1974) have shown increased firing rate in hepatic vagal afferents in response to changes in Na concentration comparable with those used in these studies. The alternative explanations, that changes in discharge rate were initiated by changes in ionic gradients or conductances alone seem less tenable. The three situations (increased Na outside, ouabain, and EDTA) in which an increased receptor activity was assumed to occur could have been associated with increased Na influx relative to efflux independent of pump activity. However, in the first case, the smallness of the increase in external Na makes unlikely any changes in membrane potential based on change in internal Na concentration or conductance. The opposing or hyperpolarizing effect of elevating external K seems equally unlikely to be attributable to an increased K conductance (Marmor & Gorman, 1970). The glucose receptor would have to be totally independent, which may be the case (Adachi et al. 1976), but this remains to be proved for the in vivo model. These studies were not designed to assess the physiological significance of the postulated receptors in the regulation of water and salt balance. The variable effects seen on water intake with infusions of glucose, KCI, or any of the three drugs used may have been non-specific, i.e. an inconsistent and generalized behavioural response to a 'disturbing' experience, especially when decreased water intake occurred with decreased saline intake to decrease total fluid drink. Even the clear-cut decreased water intake associated with increased saline intake (as with HP infusion of 2 Mglucose or VC infusion of 32 mM-KCl in 0 15 m-NaCl) may have been non-specific in the sense that water intake was neglected if saline drinking was stimulated. The counter argument that saline intake was increased by depression of water intake seems untenable in view of the frequent suppression of water intake without increase in saline intake. For these reasons, the postulated receptors are believed to be acting on a saline drinking controller rather than a water drinking controller. However, further experiments on the drinking of aversive, hypertonic NaCl solutions under conditions of Na depletion would be required before any firm conclusions regarding receptor action specificity could be made. This work was supported in part by NSF grant GM 13810.

138

W. D. BLAKE AND K. K. LIN

REFERENCES ADACHI, A., NIIJIMA, A. & JACOBS, H. L. (1976). An hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioural studies. Am. J. Phy8iol. 231, 1043-1049. ARMED, K. & JuDAH, J. D. (1964). Preparation of lipoproteins containing cation-dependent ATPase. Biochim. biophy8. Acta 93, 603-613. ANDREWS, W. H. H. & ORBACH, J. (1973). A study of compounds which initiate and block nerve impulses in the perfused rabbit liver. Br. J. Pharmac. Chemother. 49, 192-204. ANDREWS, W. H. H. & ORBACH, J. (1974). Sodium receptors activating some nerves of perfused rabbit livers. Am. J. Phyeiol. 227, 1273-1275. BOYD, J. E. & MuLRow, P. J. (1972). Further studies of the influence of potassium upon aldosterone production in the rat. Endocrinology 90, 299-301. CHAMBAUT, A., LERAY-PECKER, F., FELDMAN, G. & HANOUNE, J. (1974). Calcium-binding properties and ATPase activities of rat liver plasma membranes. J. gen. Physiol. 64, 104126. DALY, J. J., ROE, J. W. & HORROCKS, P. (1967). A comparison of sodium excretion following the infusion of saline into systemic and portal veins in the dog: evidence for a hepatic role in the control of sodium excretion. Clin. Sci. 33, 481-487. DEN HERTOG, A., GREENGARD, D. & RITCHIE, J. M. (1969). On the metabolic basis of nervous activity. J. Physiol. 204, 511-521. DENTON, D. A. (1966). Some theoretical considerations in relation to innate appetite for salt. Cond. Reflex 1, 144-170. DENTON, D. A., KRAINTz, F. & KRAINTZ, L. (1970). The inhibition of salt appetite of sodium deficient sheep by intracarotid infusion of ouabain. Comm. Behav. Biol. 5, 183-193. DE WEER, P. (1970). Effects of intracellular adenosine-5-diphosphate and orthophosphate on the sensitivity of sodium efflux from squid axon to external sodium and potassium. J. gen. Phyeiol. 56, 583-620. HABREICH, F. J. (1968). Osmoreception in the portal circulation. Fedn Proc. 27, 1137-1141. KERKUT, G. A. & YORK, B. (1971). The Electrogenic Sodium Pump. Bristol: Scientechnica Ltd. KUNZE, D. L., SAUM, W. R. & BROWN, A. M. (1977). Sodium sensitivity of baroreceptors mediates reflex changes of blood pressure and urine flow. Nature, Lond. 267, 75-78. LARSEN, J. A., KRARUP, N. & MUNCK, A. (1976). Liver hemodynamics and liver function in cats during graded hypoxic hypoxemia. Acta phyeiol. scand. 98, 257-262. LIN, K. K. & BLAKE, W. D. (1971). Hepatic sodium receptor in control of saline drinking behaviour. Comm. Behav. Biol. 5, 359-363. LIvENGOOD, D. R. & KusANO, K. (1972). Evidence for an electrogenic sodium pump in follower cells of the lobster cardiac ganglion. J. Neurophysiol. 35, 170-186. MARMOR, M. F. & GORMAN, A. L. F. (1970). Membrane potential as the sum of ionic and metabolic components. Science, N.Y. 167, 65-67. Mouw, D. R. & VANDER, A. J. (1970). Evidence for brain Na receptors controlling renal Na excretion and plasma renin activity. Am. J. Physiol. 219, 822-832. NiiJiMA, A. (1969a). Afferent discharges from osmoreceptors in the liver of the guinea pig. Science, N.Y. 166, 1519-1520. NIIJIMA, A. (1969b). Afferent impulse discharges from gluco-receptors in the liver of the guinea pig. Ann. N.Y. Acad. Sci. 157, 690-700. PASSO, S. S., THORNBOROUGH, J. R. & ROTHBALLER, A. B. (1973). Hepatic receptors in control of sodium excretion in anesthetized cats. Am. J. Physiol. 224, 373-375. PoTKAY, S. & GILMORE, J. P. (1970). Renal responses to vena cava and portal venous infusions of sodium chloride in unanesthetized dogs. Clin. Sci. 39, 13-20. RANG, H. P. & RITCHIE, J. H. (1968). On the electrogenic sodium pump in mammalian nonmyelinated nerve fibres and its activation by various external cations. J. Physiol. 196, 183221. RussEK, M. (1970). Demonstration of the influence of an hepatic gluco-sensitive mechanism on food intake. Physiol. & Behav. 5, 1207-1209. SAUM, W. R., BROWN, A. M. & TULEY, F. H. (1976). An electrogenic sodium pump and baroreceptor function in normotensive and spontaneously hypertensive rats. Circulation Ree. 39, 497-505.

SALINE DRINKING CONTROL

139

SCHNEIDER, E. G., DAVIS, J. O., ROBB, C. A., BAUMBER, J. S., JOHNSON, J. A. & WRIGHT, F. S. (1970). Lack of evidence for a hepatic osmoreceptor mechanism in conscious dogs. Am. J. Phy8iol. 218, 42-45. SJODTN, R. A. (1971). The kinetics of sodium extrusion in striated muscle as functions of the external sodium and potassium ion concentrations. J. gen. Phy8iol. 57, 164-187. SOKOLOVE, P. G. & COOKE, I. M. (1971). Inhibition of impulse activity in a sensory neuron by an electrogenic pump. J. gen. Phy8iol. 57, 125-163. STEPHENS, D. B. & BALDWIN, B. A. (1974). The lack of effect of intrajugular or intraportal injections of glucose or amino-acids on food intake in pigs. Physiol. & Behav. 12, 923-929. STRANDJOY, J. W. & WILLIAMSON, H. E. (1970). Evidence for an hepatic role in the control of sodium excretion. Proc. Soc. exp. Biol. Med. 133, 419-422. Tsm, T. L. (1958). A histological study of sensory nerves in the liver. Aca neuro. 17, 354-385. WOLF, G., MCGOVERN, J. F. & DICARA, L. V. (1974). Sodium appetite: some conceptual and methodologic aspects of a model drive system. Behav. Biol. 10, 27-42.

Hepatic portal vein infusion of glucose and sodium solutions on the control of saline drinking in the rat.

129 J. Physiol. (1978), 274, pp. 129-139 With 4 text-figurea Printed in Great Britain HEPATIC PORTAL VEIN INFUSION OF GLUCOSE AND SODIUM SOLUTIONS O...
1MB Sizes 0 Downloads 0 Views