Electrophysiological investigation of neurones in sacral segments of the spinal cord was performed in [alpha]-chloralose-anaesthetized cats in order to establish whether at least some ascending tract neurones could diverge to three different centres located in the brainstem, the cerebellum or the spinal cord. Recordings of antidromic action potentials from cells in S1 and S2 segments were taken following stimulation of the contralateral gigantocellular nucleus, contralateral restiform body and ipsi- and contralateral grey matter of the C6 spinal segment. Antidromic responses allowed identification of several types of neurones that differed in their pattern of supraspinal or propriospinal projections. In eighteen out of a total of sixty-three neurones triple projections to all the above structures were found. In the majority of cells investigated their axons divided into two branches ascending both ipsi- and contralaterally in the lateral funiculi of the spinal cord. Their cell bodies were distributed in laminae VII-VIII except for a minor group of neurones that projected to the C6 segment only, which were located in laminae V-VI. The latter group also displayed lower values of axonal conduction velocities. Comparison of conduction velocities in proximal and distal parts of axons revealed significant slowing in most, raising the possibility that additional collaterals were present to other spinal or supraspinal centres. Dual and triple projections from most cells in this study suggest that such a divergence may be a more common feature of ascending tract neurones than has been reported before.

A disturbed calcium homeostasis characterizes diabetic pregnancy. This study documents changes in bone mineral composition in diabetic pregnant rats and examines the effect of insulin replacement. Control pregnant (CP), diabetic pregnant (DP) and insulin-treated DP (DPi) rats were assessed for femoral calcium and magnesium content, bone mineral density (BMD) and the ratio of hypertrophic to maturing and proliferative cells in the femoral growth plate. DP rats showed a significantly (P < 0·01) lower body weight, femoral weight and length than CP rats. Femoral calcium and magnesium content was also significantly (P < 0·05) lower in DP rats, as was ash weight. When calcium and magnesium were normalized for ash weight no signficant differences were apparent. A significantly (P < 0·05) lower total BMD at the distal femur was seen in DP rats. This comprised a significantly (P < 0·01) lower trabecular BMD with no significant change in cortical BMD. A significantly (P < 0·05) higher ratio of hypertrophic to maturing and proliferative cells of the femoral growth plate was evident in DP animals. DPi rats showed normal blood glucose concentrations and femoral growth plate histology. DPi rats also showed normal femoral weight and length but only partially restored femoral ash weight and mineral content. Insulin failed to normalize total or trabecular BMD. Diabetes mellitus clearly has a marked effect on bone growth and mineral content in pregnancy which may be relevant to overall calcium homeostasis. The lower bone growth, bone calcium content and trabecular BMD may be unfortunate consequences of the marked hypercalciuria reported elsewhere in diabetes and may serve to maintain normocalcaemia in the disease.

The relative contribution of intraluminal versus peritubular factors in mediating glomerulo-tubular balance (GTB) is still controversial. We modulated the load of tubular fluid to the proximal tubule of single nephrons of rats by injecting oil into the efferent arteries (EAO). In fifty nephrons the changes in reabsorption induced by obstruction occurred in the same direction as, and were significantly correlated with, the simultaneous changes in single nephron glomerular filtration rate (SNGFR) (y = -0·54 + 0·92x, R = 0·91, P < 0·0001). In an additional set of thirty-nine nephrons the load of tubular fluid was changed, during EAO, by partial collection from Bowman's space or from the early proximal convolution. Thus, the rate of tubular fluid delivery along the proximal tubule was changed in an experimental situation that prevented any modification in the oncotic pressure of peritubular capillaries. The changes in proximal deliveries during this experimental condition were significantly correlated with those during reabsorption (y = -2·87 + 0·71x, R = 0·82, P < 0·0001). These data demonstrate that GTB is fully expressed even when the native peritubular environment is kept constant while the rate of perfusion of proximal tubular segments with native tubular fluid is changed.

This study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N[omega]- nitro-L-arginine methyl ester (L-NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L-arginine. In the present study, we show that D-arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L-arginine. Another NOS inhibitor, NG -nitro-L-arginine (L-NOARG), produced similar effects which were not reversed by L-arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L-NAME, reduced the increase in atrio-ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the 'paced' and 'unpaced' heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate-limiting factor in the cardiac responses to vagal stimulation.

We have investigated the effect of temperature upon the rate-dependent decrease in the L-type Ca2+ current (iCa) in isolated rat ventricular myocytes. Increasing the rate of stimulation from 0·5 to 3·0 Hz for 30 s induced a reversible decrease in iCa which was temperature dependent. Compared to control (0·5 Hz), the first beat at 3 Hz was decreased by 38 ± 7 % at 22¡C and by 9 ± 1 % at 37¡C (mean ± S.E.M., n = 5, P < 0·05) and, after 30 s of 3 Hz stimulation, iCa was reduced by a further 26 ± 4 and 21 ± 2 % at 22 and 37¡C, respectively. The magnitude of this secondary decline was not significantly different at the two temperatures (P = 0·29). Corroboratory results were obtained from cell-attached patches which also illustrated that the rate-dependent decrease in iCa resulted from a reduction of open channel probability. Paired pulse experiments showed that the greater initial rate-dependent decrease in iCa at 22¡C occurred as a result of slower recovery from fast inactivation processes at 22 than at 37¡C. Recovery of the channel from fast inactivation was very temperature sensitive with a Q10 of 5·6. In contrast, the secondary, progressive decrease in iCa, which results from incomplete recovery from ultra-slow voltage-dependent inactivation, was similar at the two temperatures and appears to be much less temperature dependent.

Experiments were performed on twenty-two neurologically normal subjects in order to investigate the effects of skin brushing on H reflex excitability in triceps surae. H reflex amplitude was observed to decrease during brushing of a 2 cm × 10 cm area of skin overlying triceps surae, returning to control levels when brushing ceased. Alterations in the duration of the brushing period did not affect the magnitude of the H reflex inhibition, although increased frequency of brush strokes per minute slightly increased the amount of inhibition observed. Brushing of smaller skin areas overlying the muscle only sometimes resulted in H reflex inhibition. Brushing over other skin areas of the lower limb produced only slight effects on triceps surae H reflex amplitude. Removal of cutaneous input from the skin overlying triceps surae abolished any effects of brushing in this area on H reflex amplitude. These results demonstrate an inhibitory effect of brushing on H reflex excitability in normal subjects. If such results are confirmed in subjects with neurological deficit, they could have implications for the use of brushing in clinical practice.

Gut endocrine cells possess the capacity to take up and decarboxylate biogenic amine precursors. Decarboxylation is mediated by aromatic L-amino acid decarboxylase (AADC) which is encoded by mRNAs differing in their 5' untranslated regions (UTR) depending on the usage of alternative first exons, 1a and 1b, each with its own acceptor site (-13 and -8 bases relative to the translation start site, respectively). We describe here a novel splice variant of exon 1a-AADC mRNA in rat antral mucosa. Both exon 1a and 1b mRNAs were expressed in rat antral mucosa, but the 1a form was spliced into the acceptor site usually associated with exon 1b (-8). An enteroendocrine cell line (STC-1) expressed exon 1a or exon 1b mRNAs spliced into the -8 acceptor site of exon 2. Transient transfection of a range of cell lines with reporter constructs revealed that all three 5' UTRs efficiently supported expression of the Luciferase reporter. There is therefore a novel, functional 5' UTR of AADC mRNA in rat antral mucosa; alternative AADC splice variants could provide the capacity for control at the level of mRNA translation.

Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0·01, ANOVA). Mean action potential duration at 90 % repolarization (APD90) was 237 ± 8 ms in subendocardial (n = 30 myocytes), 251 ± 7 ms in midmyocardial (n = 30) and 204 ± 7 ms in subepicardial myocytes (n = 36). L-type calcium current (ICa) density and background potassium current (IK1) density were similar in the three regions studied. Delayed rectifier current (IK) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean IK density (after a step to +80 mV) was larger in subepicardial myocytes (1·59 ± 0·16 pA pF-1, n = 16) than in either subendocardial (1·16 ± 0·12 pA pF-1, n = 17) or midmyocardial (1·13 ± 0·11 pA pF-1, n = 21) myocytes (P < 0·05, ANOVA). The La3+-insensitive current (IKs) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (IKr) was greater in subepicardial (0·50 ± 0·04 pA pF-1, n = 11) than in subendocardial (0·25 ± 0·05 pA pF-1, n = 9) or in midmyocardial myocytes (0·38 ± 0·05 pA pF-1, n = 11, P < 0·05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0·1 µM tetrodotoxin (TTX). TTX-induced shortening of APD90 was greater in subendocardial myocytes (35·7 ± 7·1 %, n = 11) than in midmyocardial (15·7 ± 3·8 %, n = 10) and subepicardial (20·2 ± 4·3 %, n = 11) myocytes (P < 0·05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from guinea-pig left ventricle are attributable, at least in part, to differences in IK and Na+-dependent currents.

After 2 months of streptozotocin-induced diabetes in rats, the membrane potential of the diaphragm muscle when measured in vitro at 30¡C was unchanged but the tetanic tension, the half-relaxation time of the isometric twitch and the fatigue resistance were each reduced. Treatment of the diabetic rats with the antihyperglycaemic agent metformin prevented the decrease in half-relaxation time and the greater degree of fatigue in the diaphragms. The possibility that changes in H+ and cyclic AMP concentrations in the diabetic muscles contributed to the decreased contractile function and that metformin acted by attenuating these changes is discussed.

Hypoxic pulmonary vasoconstriction (HPV) may be mediated, in part, by an oxygen-sensing mechanism intrinsic to pulmonary arterial smooth muscle. It has been proposed that hypoxia inhibits a K+ conductance, which promotes membrane depolarization, subsequent activation of L-type Ca2+ channels and ultimately constriction. We have monitored hypoxia-induced changes in the intracellular Ca2+ concentration ([Ca2+]i) of single myocytes isolated from the rat pulmonary arterial tree using microspectrofluorimetry and ratiometric measurement of indo-1 fluorescence. The basal level of [Ca2+]i was in the range 35-80 nM and cells were quiescent at rest exhibiting no spontaneous oscillations in [Ca2+]i. When the extracellular K+ concentration ([K+]o) was raised to 20 mM, the [Ca2+]i increased from [similar]60 to [similar]100 nM. This increase was abolished by nifedipine, demonstrating the presence, and need for activation, of functional voltage-gated L-type Ca2+ channels. Hypoxia (PO2 [less than or equal to] 30 mmHg; throughout) had little effect on the resting [Ca2+]i in myocytes isolated from either the main intrapulmonary artery, or its primary, secondary or tertiary branches. However, upon raising the [Ca2+]i by increasing [K+]o to 20 mM, hypoxia was found to lower [Ca2+]i, from [similar]110 to [similar]70 nM, in cells isolated from the main conduit and primary branches of the intrapulmonary artery. In marked contrast, when [Ca2+]i was raised, by increasing [K+]o to 20 mM, in myocytes isolated from secondary and tertiary branches of the intrapulmonary artery, hypoxia induced a further reversible increase in the [Ca2+]i from [similar]160 to [similar]240 nM. Neither hypoxia alone nor in combination with 20 mM K+o induced any increase in the [Ca2+]i in the presence of nifedipine. We conclude that hypoxia may modulate [Ca2+]i in rat pulmonary artery myocytes only following its elevation by a depolarizing stimulus.

The passive and active electrical properties of left ventricular myocardium were measured, using conducted action potentials and current clamp of isolated myocytes. The objective was to quantify changes of intracellular resistivity, Ri, during hypertrophic growth and the simultaneous imposition of cellular hypoxia. Ri was estimated from the time course of the rising phase of a conducted action potential using a solution of the two-dimensional cable equation. The thoracic aorta of guinea-pigs was constricted to induce left ventricular hypertrophy (LVH) and myocardium used 50 and 150 days post-operation. Conduction velocity increased in the earlier stage of LVH and declined in the later stage, compared with age-matched controls. Hypoxia reduced conduction velocity in all experimental groups. Ri increased only in the later stage of hypertrophy (253 ± 39 [Omega] cm to 544 ± 130 [Omega] cm) and was additionally increased by hypoxia in all groups (e.g. control myocardium 252 ± 39 [Omega] cm to 506 ± 170 [Omega] cm). The magnitude of the increase of Ri in hypertrophied, hypoxic myocardium can create conditions required to generate re-entrant arrhythmias.

We investigated the effects of glucose 6-phosphate (G6P) on skeletal muscle contractile apparatus and sarcoplasmic reticulum (SR) function. Using rat extensor digitorum longus fibres, the presence of 5 mM G6P decreased the Ca2+ sensitivity of both force production and actomyosin ATPase (AM-ATPase) activity. Conversely, maximal Ca2+-activated force was unaffected while maximal AM-ATPase activity was increased by 37 %. In SR vesicles isolated from rat gastrocnemius, G6P markedly altered Ca2+ handling. It increased Ca2+-stimulated Ca2+-ATPase activity but depressed the net rate of Ca2+ uptake. This latter effect appears to be due to G6P-stimulated Ca2+ release. When G6P was added to Ca2+-loaded vesicles, a small, transient release of Ca2+ was elicited. In addition, G6P lowered the threshold for Ca2+-induced Ca2+ release but depressed the net rates of both AgNO3- and caffeine-induced releases. It is possible that the accumulation of G6P during muscular activity may adversely affect muscle force production and contribute to the fatigue process via its action on the contractile apparatus and SR.

This series of papers is presented as a tribute to Wilfred F. Widdas, Emeritus Professor, Bedford and Royal Holloway College, University of London. The papers are the outcome of a meeting held by the Physiological Society on January 5th 1997 at Sheffield as a celebration of Widdas's scientific work. The work referred to of course is the series of papers by Widdas and co-workers describing mediated transfer of sugars across cell membranes. The ideas therein relating to carrier-mediated transport of sugars across membranes have become one of the most influential scientific paradigms in modern biology. The history of science shows that a successful paradigm has its supporters, who work either to extend its influence to ever wider spheres, or to understand the nature of its constraints. The natural tendency is for this support group to diminish the importance of anomalous results; this consequently breeds an opposition group whose aim is to show that these anomalies require major adjustments to the paradigm. This arrangement leads to the formation of scientific factions and eventually either to the overthrow of the paradigm or to a major reconstruction and thus scientific advances. A special feature of sugar transport is the relative scientific longevity of the workers in the field, of whom Widdas is a prime example; a similar tendency was found in quite a few of the participants at the meeting. Another is that they do not fall easily into the facile categories of supporters or adversaries of the carrier paradigm. Although Wilfred Widdas's early work led both to the formation and refinement of the carrier molecule, he always has had a more open view about the nature of the transporter than many of its more ardent supporters. His indefatigable scientific curiosity has led him to investigate some nagging anomalies in the theory of glucose transport and consequently somewhat away from the mainstream. This rare and courageous stance stems, perhaps, from the Non-Conformist tradition from which he comes and certainly demonstrates a monumental dedication to science. All the participants are grateful to the Physiological Society and Glaxo-Wellcome for their financial support and the editors of Experimental Physiology for their help in testimonial publication.

Potassium transport was measured in isolated chicken colonocytes using 85Rb+ as a tracer for K+. Rb+ was determined by atomic absorption spectrometry. The results revealed that net K+ uptake occurred via at least four mechanisms: (i) Na+,K+-ATPase, (ii) K+-ATPase, (iii) Na+-K+-2Cl- cotransport system and (iv) a mechanism(s) which is resistant to both ouabain and bumetanide. The rate of K+(Rb+) efflux is stimulated by the calcium ionophore A23187, inhibited by either quinine, verapamil or Ba2+, and unaffected by either apamin, 3,4-diaminopyridine (3,4-DAP), H2-DIDS or bumetanide. The A23187-induced increase in K+(Rb+) efflux was abolished by apamin. These findings suggest that K+(Rb+) efflux from chicken colonocytes occurs at least in part through Ca2+-activated K+ channels. The present results also show that all these K+ transport systems are involved in cell volume regulation. Thus, external hyposmolarity decreased net K+(Rb+) uptake mediated by Na+,K+-ATPase, K+-ATPase and the Na+-K+-2Cl- cotransporter and increased K+(Rb+) efflux rate. The opposite was observed under hyperosmotic conditions.

Exposure of cardiac muscle to metabolic poisons reduces the availability of cellular ATP and cardiac dysfunction ensues. In this study rat ventricular myocytes were exposed to 2-deoxyglucose, iodoacetate and cyanide to induce complete metabolic blockade. Changes in contraction, cytosolic Ca2+ and pH were determined during metabolic blockade and following restoration of mitochondrial ATP production. Metabolic blockade resulted in a rapid failure of contractions and Ca2+ transients, a rise of diastolic Ca2+, a cytosolic acidosis and ultimately a rigor contracture. Washing out cyanide during the development of the rigor contracture led to a rapid relaxation of the contracture, a fall in cytosolic Ca2+ and a rapid, partial reversal of the cytosolic acidosis. The partial reversal of the cytosolic acidosis and fall of cytosolic Ca2+ were abolished in the presence of oligomycin. This suggests that the rapid partial recovery of cytosolic acidosis could result from the rephosphorylation of ADP to ATP by the mitochondrial F1,F0-ATPase (a reaction that consumes protons).

The aim of this study was to determine the ouabain receptor density, Na+,K+-ATPase function and contractile properties of cardiac muscle in insulin-dependent and non-insulin-dependent rat diabetes mellitus (IDDM and NIDDM, respectively) and the reversibility of the diabetes-induced changes by insulin or thyroxin substitution. IDDM and NIDDM were induced in Wistar rats by streptozotocin injection. Contractile parameters were measured in isolated left ventricular trabeculae. [3H]Ouabain binding to myocardium was measured in right and left ventricular strips obtained from diabetic animals and their age-matched controls. Both the maximum [3H]ouabain binding capacity (Bmax) and the Kd for [3H]ouabain binding, as well as maximum 86Rb+ uptake and rate of contraction, were decreased in IDDM myocardium compared with controls. Insulin or thyroxin substitution reversed the reduction in Bmax and contraction rate, but not the decrease in Kd. In young, but not old, control animals, both Bmax and maximum 86Rb+ uptake were higher in the right ventricular myocardium than in the left one. In contrast to changes observed in IDDM, both Bmax and Kd for [3H]ouabain binding were increased in the left but not in the right ventricle of NIDDM animals. NIDDM caused no alterations in contractile properties. Prominent differences were observed in [3H]ouabain binding characteristics and myocardial contractility between young and old control animals. Bmax of [3H]ouabain binding and rate of contraction were inversely proportional in all preparations studied. It is concluded that IDDM and NIDDM induce different alterations in myocardial Na+,K+-ATPase, and these changes may influence the contractile properties of cardiac muscle.

We studied the development of nutritional iron deficiency 0, 10, 20, 30 and 40 days after the intake of a semisynthetic diet lacking iron (diet 0) and the possible interactions with calcium, phosphorus and magnesium in both control rats and rats after 40 days of iron deficiency. During this period, iron deficiency was found to produce stress in the rats, as evidenced by high levels of cortisol in the serum. High levels of parathyroid hormone (PTH) were also found. There was a considerable increase in the absorption of calcium, phosphorus and magnesium, but the phosphorus and magnesium balance decreased and that of calcium remained practically unchanged, although there was an increase in calcium urinary elimination. Despite the noticeable degree of bone demineralization, which was evident in the femur, serum levels of calcium, phosphorus and magnesium remained constant. The present study shows that severe nutritional ferropenic anaemia provokes significant alterations in the metabolism of calcium, phosphorus and magnesium. We conclude that these alterations should be taken into account in the treatment of this pathology, given its prevalence and the fact that it may exacerbate other pathologies, particularly those related to the metabolism of calcium and phosphorus.

To elucidate the role of corticotrophin-releasing factor (CRF) in the spontaneous rhythmic contractions of pregnant myometrium, isometric contractions of longitudinal myometrial preparations taken from Sprague-Dawley rats (18-21 days gestation) were measured. CRF (0·03-30 nM) significantly increased the amplitude (117 ± 4 % of control at 30 nM, mean ± S.E.M.) and significantly decreased the frequency (74 ± 5 %) in a concentration-dependent manner. The area under the tension curve did not increase (89 ± 8 %). Such effects of CRF were not observed in preparations pretreated with the RP diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS, 10 µM), an inhibitor of protein kinase A. In preparations pretreated with indomethacin (1 µM), CRF caused little change in the amplitude but significantly decreased the frequency of the contractions. Intracellular cAMP levels in the preparations, measured by enzyme immunoassay, rose when CRF was applied at 30 nM. These results suggest that the slight positive inotropic action of CRF is due to activation of both cAMP and prostaglandin pathways, whereas the negative chronotropic action is due solely to the cAMP signalling pathway.

This series of papers is presented as a tribute to Wilfred F. Widdas, Emeritus Professor, Bedford and Royal Holloway College, University of London. The papers are the outcome of a meeting held by the Physiological Society on January 5th 1997 at Sheffield as a celebration of Widdas's scientific work.

The work referred to of course is the series of papers by Widdas and co-workers describing mediated transfer of sugars across cell membranes. The ideas therein relating to carrier-mediated transport of sugars across membranes have become one of the most influential scientific paradigms in modern biology.

The history of science shows that a successful paradigm has its supporters, who work either to extend its influence to ever wider spheres, or to understand the nature of its constraints. The natural tendency is for this support group to diminish the importance of anomalous results; this consequently breeds an opposition group whose aim is to show that these anomalies require major adjustments to the paradigm. This arrangement leads to the formation of scientific factions and eventually either to the overthrow of the paradigm or to a major reconstruction and thus scientific advances.

A special feature of sugar transport is the relative scientific longevity of the workers in the field, of whom Widdas is a prime example; a similar tendency was found in quite a few of the participants at the meeting. Another is that they do not fall easily into the facile categories of supporters or adversaries of the carrier paradigm. Although Wilfred Widdas's early work led both to the formation and refinement of the carrier molecule, he always has had a more open view about the nature of the transporter than many of its more ardent supporters. His indefatigable scientific curiosity has led him to investigate some nagging anomalies in the theory of glucose transport and consequently somewhat away from the mainstream.

This rare and courageous stance stems, perhaps, from the Non-Conformist tradition from which he comes and certainly demonstrates a monumental dedication to science.All the participants are grateful to the Physiological Society and Glaxo-Wellcome for their financial support and the editors of Experimental Physiology for their help in testimonial publication.

The present study was carried out to determine whether the increased salt intake induced by increased specific sodium appetite in pregnant rats modifies water-salt homeostasis throughout pregnancy. Two groups of pregnant rats were used, one fed ad libitum with a normal sodium (NS) diet consisting of standard rat chow and distilled water, and the other fed with a high-sodium (HS) diet with free access to chow, distilled water plus saline solution (1·5 % NaCl). Virgin rats in dioestrus were also studied as non-pregnant controls. Pregnant animals were studied on days 4, 9, 14, 20 and 21 of gestation at which time body weight, water and saline intake, sodium excretion, plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) concentrations, as well as plasma osmolality were determined. Data showed that water intake was higher in the NS group, but total fluid intake (water plus saline) was higher in the HS group throughout pregnancy. Dietary sodium intake was the same for both groups but total sodium intake (chow plus saline) was 60-98 % higher in the HS rats. Pregnant HS rats excreted more fluid (35-50 %) and sodium (up to 100 %) compared with NS rats, indicating that the animals could change their renal excretion in response to a 2·5-fold higher dietary sodium intake compared with the control level. Salt satiety during pregnancy did not modify plasma ANP concentration. In both groups of pregnant rats ANP levels increased 3-fold on day 14 without significant alteration in sodium excretion, suggesting that the natriuretic action of ANP is attenuated at least after the second week of pregnancy. High sodium intake did not change plasma AVP concentration or osmolality and both groups showed the same gradual decrease in plasma osmolality ([similar]8 mosmol kg-1) at the end of pregnancy that was not accompanied by decreased plasma AVP concentration. The present data show that rats maintain the special homeostatic equilibrium that occurs in normal pregnancy even when they are allowed to increase sodium intake to satisfy their salt appetite during this period of the reproductive cycle.