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Nitric oxide (NO) is a gas molecule to signal neurotransmission in the hypothalamo-neurohypophysial system during osmotic regulation. We previously reported that osmotic stimulation increased nitric oxide synthase (NOS) activity in the supraoptic nuclei (SON) and neural lobe. The aim of this study is to define the role of NO in the regulation of Ca(2+)-activated K(+) channels (BK channels) expression in the magnocellular system following dehydration. We used Western blot analysis and quantitative immunocytochemistry to conduct the experiment in rats. In the immunoblot study, we found that water deprivation significantly increased the expression of BK channels in the SON and neural lobes. Dehydration also enhanced the profiles of neurons expressing vasopressin and oxytocin significantly. In about 70% of these neurons, BK channels were co-localized in the same neuron, and their expression increased significantly during dehydration. We further examined the effects of intracerebroventricular administration of sodium nitroprusside (a donor of NO) and L-NAME (an inhibitor of NO synthase) on expression of BK channels in the SON. We found that compared to animals treated with the donor of NO, there were significant decreases in the expression of BK proteins in animals receiving L-NAME. These results suggest that NO may enhance the expression of BK channels in the supraoptic nuclei and neural lobe of rats following dehydration.

Magnocellular neurons are innervated by an excitatory histaminergic pathway. They also express neuronal NO synthase, interleukin-1beta (IL-1beta) and cyclo-oxygenase (COX). In normally hydrated rats when NO synthase activity is inhibited with N(G)-nitro-L-arginine methyl ester (L-NAME), administered intracerebroventricularly (i.c.v.), OT concentration in plasma increases. In the present study, the increase in hormone after L-NAME is attenuated by indomethacin, an inhibitor of COX, as well as by antagonists of histamine receptors at H1 (pyrilamine) and H2 (cimetidine) subtypes injected i.c.v. Moreover, enhanced OT secretion induced by centrally administered IL-1beta, but not naloxone (opiate receptor antagonist), is prevented by indomethacin. PGE2 and PGD2 (i.c.v.) stimulate OT release, but only PGD2 affects circulating vasopressin levels. Thus, NO inhibits release of OT stimulated by: (1) a COX-dependent mechanism, i.e. NO---(COX--+PG--+OT release); (2) histamine, i.e. NO---(histamine--H1 and H2 receptors--+OT release); and possibly (3) IL-1beta, i.e. NO---(IL-1beta--+COX--+PG--+OT release). These interactions of NO, cytokine and histamine may be important for management of stress-induced activation of neuroendocrine systems.

SUMMARY 1. Magnocellular neurons, which release oxytocin (OT) or vasopressin (VP) into the circulation in response to hyperosmolality, hypovolaemia and cholecystokinin (CCK), undergo a resetting during pregnancy and lactation that involves circumventricular organs. 2. During gestation, there is a similar lowering of the osmotic thresholds for stimulation of OT and VP release, whereas the responsiveness of both neuroendocrine systems to hyperosmolality is attenuated by lactation. These osmotic changes in the magnocellular system are mediated by depletion of hormone (OT) stores in the neurohypophysis (lactation), as well as by alterations in afferent stimulation via pathways involving the subfornical organ, organum vasculosum lamina terminalis and median preoptic nucleus. 3. During gestation, both the VP and OT systems are reset such that the expanded blood volume is maintained and defended as ‘normal’ in response to hypovlaemia. Thus, in virgin animals, only a 0–5% reduction in blood volume is needed to activate VP release, whereas 23–25% is required for stimulation of the oxytocinergic system. Thereafter, incremental changes in plasma levels of both hormones with increasing loss in blood volume are similar in virgin and pregnant animals. However, during lactation, the apparent hypovolaemic threshold for both hormones becomes significantly elevated to 20.4% (VP) and > 25% (OT) blood volume depletion, resulting in a decreased responsiveness of the magnocellular system to hypovolaemia. 4. The OT response to CCK is attenuated in lactating animals and circulating VP is unaffected in pregnant rats given the peptide.

N G-nitro-l-arginine methyl ester (l-NAME; 250 μg/5 μl), an inhibitor of NO synthase, or the vehicle artificial cerebrospinal fluid (aCSF; 5 μl) was administered intracerebroventricularly to conscious rats hemorrhaged (0.7 ml/min) to a 20% volume depletion. Hypotension was maximal 5 min after hemorrhage ended, with compensatory recovery to basal levels 20 min later, regardless of drug treatment.l-NAME, however, elevated ( P < 0.05) blood pressure (vs. aCSF controls) 40–45 min after intracerebroventricular administration. In normovolemic rats, l-NAME produced a significant pressor response and increased plasma levels of vasopressin (VP) and oxytocin (OT). After hemorrhage, both hormone levels increased, but only OT was further enhanced byl-NAME. Thus centrally produced NO tonically inhibits OT and VP secretion under basal normovolemic conditions and selectively inhibits OT release during hypovolemia. Hemorrhage increased the rates of glucose utilization in the neural lobe, indicative of enhanced efferent neural functional activity.l-NAME further enhanced the metabolic activity in the entire hypothalamoneurohypophysial system of hemorrhaged animals. Several other brain structures involved in the regulation of blood pressure and the stress response were also metabolically affected by the hemorrhage andl-NAME.

Central inhibition of nitric oxide synthase (NOS) by intracerebroventricular (i.c.v.) administration of NG-nitro-l-arginine methyl ester (L-NAME; 150 microg/5 microl) to conscious rats produced a biphasic pressor response characterized by an initial transient increase within 5 min, and a delayed response starting between 60-90 min. The effect was stereospecific, as D-NAME (250 microg/5 microl) did not modify the resting arterial blood pressure, nor did L-arginine (323 microg/5 microl, i.c.v.), indicating the substrate for NOS is not rate-limiting. Intracerebroventricular pretreatment with losartan (25 microg/5 microl), a non-peptide antagonist of the angiotensin II AT1 receptor subtype, or indomethacin (100 microg/5 microl), a blocker of cyclooxygenase, however, prevented the initial increase in blood pressure without affecting the delayed pressor response. In contrast, neither intravenous losartan (10 mg/kg b.wt) nor prazosin, an alpha1 adrenergic receptor antagonist, at doses of 5 microg/5 microl (i.c.v.) or 0.3 mg/kg b.wt (i.v.) were effective in altering the pressor responses. These results indicate that centrally produced NO maintains the resting arterial blood pressure at least partially through modulation of the brain angiotensin system and prostaglandins.

Angiotensin II (50 ng/5 microl) and L-NAME (250 microg/5 microl), an inhibitor of NO synthase (NOS), were administered intracerebroventricularly alone or in combination to conscious rats. Mean arterial blood pressure (MABP) increased reaching a peak within 5 min in all groups compared to controls treated with the vehicle, artificial CSF (5 microl). MABP returned to basal levels at 30 min after angiotensin II and remained stable for the following 90 min. In animals treated with L-NAME alone, after the initial pressor response, MABP declined but began to increase progressively from 30 min until the end of the experiment at 120 min. When administered with angiotensin II, however, the initial pressor response was prolonged. Angiotensin II-induced drinking was significantly attenuated by L-NAME. In control rats, inhibiting NOS elevated plasma levels of oxytocin and vasopressin but in angiotensin II-stimulated animals, only oxytocin was further elevated after L-NAME. Thus, NO formed centrally inhibits basal secretion of oxytocin and vasopressin as well as the resting blood pressure. During stimulation with angiotensin II, NO facilitates drinking, limits the pressor response and selectively inhibits oxytocin release.

The drinking behavior and blood pressure responses to i.c.v. administration of artificial cerebrospinal fluid (aCSF) or NG-nitro-L-arginine methyl ester (L-NAME, 10, 250, or 500 micrograms), an inhibitor of nitric oxide synthase, were examined in conscious rats following either osmotic stimulation (1.0 M NaCl, 15 ml/kg, s.c.) or induction of hemorrhage (0.7 ml/min to a 20% blood volume loss). Water intake increased in all animals. L-NAME at doses of 250 and 500 micrograms, but not 10 micrograms, significantly attenuated water consumption induced by both stimuli. The mean arterial blood pressure (MABP), which increased after osmotic stimulation, was maintained at pressor levels by 250 and 500 micrograms of L-NAME, but decreased progressively and reached basal levels after treatment with aCSF and the lowest dose of L-NAME (i.e., 10 micrograms). Hemorrhage significantly decreased MABP in all rats. The fall in blood pressure associated with hemorrhage returned to control levels in animals treated with 250 and 500 micrograms of L-NAME but not in those treated with aCSF or 10 micrograms of L-NAME. These results indicate that nitric oxide is involved in the regulation of drinking behavior and may play an important role in the central control of blood pressure during osmotic stimulation and hypotensive hemorrhage.

Neural connections linking the four magnocellular nuclei i.e.,. the paired supraoptic (SON) and paraventricular (PVN) nuclei, may contribute to the simultaneous and parallel changes in firing patterns of oxytocinergic neurons during reflex milk ejection. To investigate these neural connections in the absence of suckling, intranuclear release of oxytocin (OT) was stimulated by microdialysis of hypertonic CSF containing 1 M NaCl (HS-CSF) into the right SON area and glucose metabolism of both SONs and PVNs and the neural lobe of virgin and lactating (10–12 day) rats was mapped by the autoradiographic [14C]deoxyglucose (DG) method. OT in the microdialysates and in plasma, obtained before and after 80–90 min of dialysis with CSF or HS-CSF, was quantified by RIA. In both virgin and lactating rats, microdialysis of HS-CSF unilaterally into the SON area significantly (p < 0.05) increased release of OT in the nucleus and into plasma, which was associated with enhanced (p < 0.05) metabolic activity in the ipsilateral and contralateral SON and the neural lobe but not in either PVN. Compared with virgins, lactating rats were less active, had lower (p < 0.05) glucose utilization in the hypothalamo-neurohypophysial system, and less (p < 0.05) OT in plasma during microdialysis of HS-CSF into the SON area. The osmotic stimulus did not activate neural structures (suprachiasmatic and medial amygdaloid nuclei) near the SON in either hemisphere. Thus, neural connections or, less likely, transport of OT via the subarachnoid space, may function to recruit activation of cells in the contralateral SON following hypertonic stimulation of cells in the other SON.

Intravenous infusion of hypertonic saline increased plasma [Na (+) ] and osmolality and induced a short-latency drinking response. These changes were associated with increased glucose utilization in the supraoptic and paraventricular nuclei and neural lobe, and decreases in the medial septum and nucleus ambiguus. The increases in glucose utilization were more accentuated in the supraoptic nuclei than in paraventricular nuclei, indicating that they are more sensitive to osmotic stimulation than the paraventricular nuclei. In association with enhanced activity in the hypothalamo-neurohypophysial system, plasma vasopressin and oxytocin concentrations increased, with a preferential increase of oxytocin over vasopressin. The hormonal contents in the neural lobe were not depleted by the osmotic stimulus despite the large increases of their concentrations in the plasma.

Intracerebroventricular (i.c.v.) administration of N G - monomethyl- l -arginine monoacetate (NMMA; 500 μg; 402 mM) and G - nitro- l -arginine methyl ester (NAME; 270 μg; 200 mM), inhibitors of nitric oxide synthase, enhanced the rise in oxytocin but not vasopressin levels in plasma of conscious rats following 24 h of water deprivation. This effect of NMMA occurred by 10 min after administration, reached its peak at 15 min and decreased by 20 min. Daily administration of lower doses (50 μg and 0.5 μ g 5 μ l , i.c.v.) of another inhibitor of nitric oxide synthase, N G - nitro- l -arginine , just before and after 24 h of water deprivation and in control animals treated similarly were without effect on either vasopression or oxytocin levels. Nitric oxide, therefore, attenuates preferentially the release of oxytocin during dehydration.

For the first time, the [ 14 C]deoxyglucose radioautographic technique has been successfully used to map physiological activity in cephalopod brains. In unilaterally blinded octopus and cuttlefish, the optic lobe of the deprived side showed a decreased uptake of the labelled tracer. This suggests that the uptake is related to functional activity. The potential of the [ 14 C]deoxyglucose technique as a powerful tool in studying the functional organization of cephalopod brains is discussed.

Denervation of sinoaortic baroreceptors in normovolemic rats selectively increases glucose utilization in the median eminence and pituitary neural lobe and enhances secretion of vasopressin and oxytocin. Hemorrhage in denervated animals increases further glucose metabolism in these structures and stimulates the release of both neurohypophysial hormones with preferentially a greater effect on vasopressin. Similar increases in glucose metabolism in these structures with a greater release of vasopressin are observed in sham-operated animals during hemorrhage. Absence of high-pressure receptors, therefore, does not modify the preferential release of vasopressin during hypovolemia. Hemorrhage also increases glucose utilization in the paraventricular and supraoptic nuclei, area postrema, and subfornical organ in sham-operated and denervated rats but only after a 20% blood reduction. The results indicate that decreased inputs from low-pressure receptors during hemorrhage increase the activity of the hypothalamoneurohypophysial system after small reductions in blood volume and that the activity of this system is tonically inhibited by baroreceptors. The activities of structures responsive to circulating angiotensin II (subfornical organ and area postrema) are stimulated by larger reductions in blood volume and their metabolic activities are not tonically influenced by high-pressure receptors.

Angiotensin infusion increased glucose metabolism in 4 of 7 subdivisions of the rat subfornical organ, the effect being stronger in ventromedial compared to dorsolateral zones across the rostrocaudal axis. [Sar1-Leu8]Angiotensin II attenuated metabolic responses to intravenous angiotensin in all subfornical organ subregions. Brattleboro rats, having high circulating levels of angiotensin, displayed greater rates of glucose metabolism than Long-Evans rats in all subregions, differences that were eliminated by captopril, an inhibitor of angiotensin converting enzyme. The studies reveal focal subfornical organ zones where in vivo metabolic activity corresponds to cytoarchitectonic evidence for topographical processing within this angiotensin-sensitive structure.

The pituitary neural lobe of homozygous Brattleboro rats has high rates of glucose utilization not affected by chronic treatment with exogenous vasopressin, despite attenuation of polydipsia and polyuria. We evaluated whether this effect may result from the inability of vasopressin to affect the hypothalamo-neurohypophysial metabolism or from the development of resistance to chronic vasopressin treatment. We used the [14C]deoxyglucose method to compare 28-h effects of vasopressin treatment (5 U/kg, i.m., twice a day) with that of desmopressin (100 micrograms/kg, i.p., once a day), a long-lasting antidiuretic hormone, on glucose utilization of the hypothalamo-neurohypophysial system and related structures in conscious homozygous Brattleboro rats. Vasopressin and desmopressin reduced water intake, plasma osmolality and plasma Na+ concentration similarly. Vasopressin decreased glucose utilization in the supraoptic nucleus, subfornical organ and median preoptic nucleus, but did not alter activity in the paraventricular nucleus and neural lobe. Desmopressin decreased glucose utilization in all these structures. The results indicate that desmopressin has a more potent inhibitory action on the hypothalamo-neurohypophysial system than vasopressin over this short duration of treatment. The lack of response in the neural lobe from chronic treatment with vasopressin seems to be due to its inability to affect the paraventricular nucleus metabolism. The maintenance of metabolic activity in the paraventricular nucleus of vasopressin-treated Brattleboro rats suggests that this structure contributes importantly to the metabolism of neural lobe.

We applied [14C]deoxyglucose autoradiography and imaging techniques to determine rates of glucose metabolism in distinct subdivisions of the subfornical organ (SFO) of conscious Brattleboro rats. Seven anatomically-defined SFO subregions were discerned having metabolic activities that differed from one another by as much as 29% in water-sated Brattleboro rats. The highest metabolic activity was found in the ventromedial zone of central and caudal subregions where previous studies identified the greatest densities of neurons, capillaries, putative angiotensin receptors, and angiotensin-immunoreactive fibers. Homozygous Brattleboro rats had rates of glucose metabolism that were 39–68% greater than those in corresponding SFO subregions of Long-Evans rats; these differences were accentuated by about 50% following 18 h of water deprivation. Exogenous treatment of Brattleboro rats with vasopressin uniformly normalized subregional glucose metabolism in the SFO. In Sprague-Dawley rats, water deprivation over 120 h provoked greater increases in metabolism of ventromedial than of dorsolateral SFO zones in amounts similar to the differences between Long-Evans and Brattleboro rats. The findings identify focal areas of high metabolic activity within subregions of the SFO where central responses are likely initiated to defend against homeostatic disturbances. The data represent further evidence for the probability that angiotensin II, as both hormone and neurotransmitter, is a metabolic stimulant of its target cells in the nervous system.

Nitric oxide (NO) is an important gas mediator in the signal transduction cascade regulating osmotic function in the hypothalamo-neurohypophysial system. We previously found that increased nitric oxide synthase (NOS) activity in the supraoptic nuclei (SON) and neural lobe following osmotic stimulation and NO could regulate the expression of Ca(2+)-activated K(+) channel (BK channels) protein in the magnocellular system during dehydration. The aim of the current study is to examine the role of NO in the regulation of nitrosocysteine and BK channel protein in the magnocellular system in dehydrated animals. Using Western blot analysis and quantitative immunofluorescent staining study, we found that water deprivation in rats significantly enhanced the expression of nitrosocysteine protein in SON and neural lobes. Immunohistochemistry study indicated that dehydration significantly increased the profiles of SON neurons co-expressing nitrosocysteine with BK-channel protein. Intracerebroventricular administration of L-NAME (an inhibitor of NO synthase) significantly reduced the neuronal profiles of nitrosocysteine, as well as their co-expression with BK-channel in SON of dehydrated rats. However, treatment of sodium nitroprusside (a donor of NO) increased this co-expression. Our results indicate that NO signaling cascade may control the expression of BK channels through the regulation of nitrosocysteine in SON and neural lobe of rats during osmotic regulation.

We tested the hypothesis that in spontaneously hypertensive rat (SHR) NO produced centrally influences the resting arterial blood pressure by attenuating mechanisms involving prostaglandins, angiotensin II, endothelin and sympathetic nervous system. L-NAME (200 micro g/5 micro l), an inhibitor of NO synthase, administered intracerebroventricularly (i.c.v.) to awake and freely moving rats increased mean arterial blood pressure (MABP) in a biphasic pattern: an early transient increase within 1 min and a late prolonged response starting at 45 min and persisting for the duration of experiment (180 min). The two pressor responses involve different neurochemical mechanisms and, based on their latencies, they appear to reflect different anatomical sites of action of L-NAME. The late, but not the early pressor response, was prevented by pretreatment with chlorisondamine (2.5 mg/kg, i.v.), a ganglionic blocker, indicating its dependence on the sympathetic nervous system. Both pressor responses were abolished by i.c.v. pretreatment with indomethacin (200 micro g/5 micro l, i.c.v.), an inhibitor of cyclo-oxygenase, showing that they are mediated by prostaglandin(s). In contrast, losartan (25 micro g/5 micro l), an angiotensin II AT(1) receptor antagonist, had no effect. The initial pressor response was also attenuated by pretreatment with the endothelin ET(A)/ET(B) receptor antagonist, PD 145065 (48 micro g/2 micro l, i.c.v.). Intravenous pretreatment with another ET(A)/ET(B) receptor antagonist, L-754,142 (15 mg/kg as a bolus+15 mg/kg/h for 180 min), however, attenuated both responses to L-NAME. It is possible that L-754,142 crossed the blood-brain barrier and blocked, in addition, central ET(A)/ET(B) receptors. These studies show that NO synthesized in the brain attenuates pressor mechanisms involving prostaglandin, endothelin and sympathetic nervous system, but not angiotensin II, to modulate resting arterial blood pressure.

Our objective was to test the hypothesis that the cGMP signal-transduction mechanism mediates nitric oxide's (NO) modulation of oxytocin (OT) and vasopressin (VP) secretion from the hypothalamo-neurohypophysial system. Three studies were conducted in adult male Sprague-Dawley rats: (1a) Euhydrated rats received an intracerebroventricular (icv) infusion (1 microl/min for 30 min) of artificial cerebrospinal fluid (aCSF), vehicle (2.6% dimethyl sulfoxide [DMSO]) or 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ) (0.05 microg/microl), an inhibitor of soluble guanylyl cyclase (sGC). ODQ did not affect basal levels of plasma VP or OT; (1b) Rats dehydrated for 24 h received aCSF or 8-Br-cGMP (icv), a membrane-permeable analog of cGMP, and plasma hormones were measured 2 min later. 8-Br-cGMP did not significantly change VP or OT levels; (2) Rats ingested water or 2% NaCl for 4 days, and NO synthase (NOS) and sGC activities were measured in posterior pituitaries, the anatomical site of hormone secretion. Salt loading enhanced (P0.001) production of [(14)C]citrulline, the coproduct of NO synthesis, without altering cGMP; (3) One SON was microdialyzed with [(14)C]arginine and NOS and sGC activities were quantified in microdialysates during intravenous (iv) infusion of isotonic or hypertonic saline in awake and anesthetized rats. In awake rats, [(14)C]citrulline recovery, but not cGMP, increased (P0.05) during intravenous infusion of both isotonic and hypertonic solutions, and after insertion of microdialysis probe itself. In anesthetized rats, however, where basal NOS activity is low, intravenous infusion of hypertonic, but not isotonic solution, increased [(14)C]citrulline recovery without affecting cGMP. Thus, in the forebrain, neither NO produced basally nor during osmotic stimulation depends on cGMP to modulate plasma vasopressin and oxytocin secretion.

Brain-derived angiotensin II (ANG II) and prostaglandins have important roles in the regulation of body fluid and blood pressure homeostasis. In the present studies we investigated the central interactions between these two neurochemical products in regulating the hypothalamo-neurohypophysial system during dehydration. Intracerebroventricular (icv) administration of prostaglandin D(2) (PGD(2); 20 microg/5 microl) to conscious adult male Sprague-Dawley rats deprived of water for 24 h did not alter significantly the already elevated plasma levels of vasopressin or oxytocin. When PGD(2) was administered in combination with losartan, an antagonist of ANG II AT(1)-receptor subtype, however, concentrations of both hormones in plasma became further elevated. Icv administration of ANG II (50 ng/5 microl) increased further the enhanced plasma levels of vasopressin and oxytocin, as expected. Pretreatment with indomethacin (200 microg/5 microl; icv), an inhibitor of cyclo-oxygenase, significantly attenuated the ANG II-induced increase in oxytocin secretion only. Independent of the presence of ANG II, however, indomethacin decreased plasma levels of vasopressin, but not oxytocin. These results indicate that a prostaglandin is required for the stimulated release of vasopressin during dehydration and that the elevation of oxytocin secretion in response to ANG II depends largely on activation of cyclo-oxygenase and production of prostaglandins. The oxytocin response to exogenously administered PGD(2), however, can be negatively modulated by a mechanism dependent upon ANG II AT(1) receptors.

Inhibiting NO synthase (NOS) with N(G)-nitro-L-arginine methyl ester (L-NAME, 250 microg/5 microl of artificial cerebrospinal fluid (aCSF)) injected intracerebroventricularly (i.c.v.) increased already enhanced levels of oxytocin, but not vasopressin, in conscious adult male Sprague-Dawley rats dehydrated for 24 h. Intracerebroventricular pretreatment with indomethacin (200 microg/5 microl aCSF), an inhibitor of cyclo-oxygenase, but not with losartan (25 microg/5 microl aCSF), an antagonist of angiotensin II (ANG II) AT(1)-receptor subtype, nearly prevented the elevation in oxytocin levels after L-NAME. Thus, NO inhibits prostaglandin (but not ANG II) mediated the modulatory actions of NO on oxytocin secretion from the hypothalamo-neurohypophysial system (HNS) during water deprivation.

1. Nitric oxide (NO) tonically inhibits the basal release of vasopressin and oxytocin into plasma. 2. Nitric oxide inhibition on vasopressin secretion is removed, while that on oxytocin is enhanced, during water deprivation, hypovolaemia, moderate osmotic stimulation and angiotensin (Ang)II. This results in a preferential release of vasopressin over oxytocin that promotes conservation of water. 3. Nitric oxide facilitates drinking behaviour stimulated by water deprivation, osmotic stimulation, haemorrhage and AngII. Together with the hormonal response, NO produces a positive water balance during reductions in intracellular and intravascular volumes. 4. Nitric oxide produced within the central nervous system maintains resting arterial blood pressure partially by attenuating the pressor actions of AngII and prostaglandins. 5. Central production of NO is enhanced during osmotic stimulation to counterbalance the salt-induced pressor response. 6. Paradoxically, central production of NO is also enhanced during haemorrhage, presumably to maintain peripheral vasodilation and blood flow to vital organs.

Intracerebroventricular (i.c.v.) injection of the inhibitor of NO synthase (NOS), N G -nitro- l -arginine methyl ester ( l -NAME) (250 μg/5 μL) attenuated the drinking response in rats deprived of water for 24 h. Moreover, oxytocin (OT) levels in plasma increased after 2 min, whereas both oxytocin and vasopressin levels were elevated at 120 min after intracerebroventricular injection. The delayed effect of l -NAME on both hormones was not observed in dehydrated animals allowed to drink water. Blood pressure remained stable after injection of artificial cerebrospinal fluid (aCSF) in dehydrated rats not allowed to drink. In rats having access to water, however, there was an immediate but transient pressor response (0–5 min) with a delayed hypotension from 45 to 120 min. l -NAME consistently increased blood pressure in a biphasic mode, whether the animals drank or not, with an early peak at 5 min that decayed after 15–30 min and a second pressor response beginning at 30–45 min and remaining elevated at 120 min when the experiment ended. These pressor responses were independent of the adrenal glands. Thus, centrally produced nitric oxide facilitates drinking, inhibits release of vasopressin and oxytocin from the magnocellular system, and maintains resting arterial blood pressure in normally hydrated and dehydrated rats.

Intracerebroventricular (I.C.V.) administration of an inhibitor of nitric oxide synthase (NOS) increases oxytocin but not vasopressin secretion, in dehydrated rats [38]. Surprisingly, central injection of L-arginine, the substrate for NOS, caused a similar effect. Kyotorphin (L-tyrosyl-L-arginine), a dipeptide formed from L-arginine by kyotorphin synthetase in the brain may mediate this magnocellular response. Therefore, the dose and time responses of hormone release were compared following I.C.V. injection of kyotorphin and L-arginine to conscious rats that were normally hydrated or deprived of water for 24 h. In water-sated rats, both L-arginine and kyotorphin increased blood pressure and plasma glucose levels coincident with elevating circulating levels of oxytocin, but not vasopressin. In dehydrated animals, both L-arginine and kyotorphin increased plasma oxytocin levels with a similar time course but only kyotorphin decreased vasopressin release. D-arginine, like L-arginine, stimulated secretion of oxytocin, indicating a nonstereospecific effect. A kyotorphin receptor antagonist (L-leucyl-L-arginine) given I.C.V. to dehydrated animals elevated plasma oxytocin and prevented the decrease in vasopressin levels after kyotorphin. Thus, kyotorphin, but not L-arginine, appears to attenuate release of vasopressin either directly from magnocellular neurons or indirectly via modulating compensatory reflexes activated by the pressor response. On the other hand, an excess of L-arginine and kyotorphin within the CNS may mimic the stress response by augmenting release of oxytocin and activating the sympathetic nervous system to increase blood pressure and plasma glucose levels.

NG-nitro-L-arginine methyl ester (L-NAME, 250 micrograms/5 microliters), an inhibitor of nitric oxide (NO) synthase, or artificial cerebrospinal fluid (5 microliters) was administered intracerebroventricularly to conscious naive rats or to rats treated subcutaneously (15 microliters/kg) with NaCl (0.15, 0.45, or 1.0 M) or given a needle prick only. Intracerebroventricular injection of L-NAME increased plasma concentration of vasopressin (VP) and oxytocin (OT) in control naive rats, indicating that NO tonically inhibits basal secretion of both hormones during isosmotic isovolemic conditions. Osmotic stimulation with hypertonic saline (0.45 and 1.0 M NaCl) elevated plasma levels of both hormones as expected. Central blockade of NO synthase further enhanced secretion of OT during mild, but not strong, osmotic stimulation, whereas the high levels of VP remained unaffected by L-NAME. In animals treated with the needle prick or 0.15 M NaCl, only OT levels were increased after L-NAME. Therefore, NO selectively inhibits OT release in response to a painful stimulus (needle prick) and moderate osmotic stimulation to promote a preferential release of VP. A transient pressor response was observed after subcutaneous injection of 0.15 and 0.45 M NaCl, but a sustained response was obtained after 1.0 M NaCl. Regardless of whether the animals received NaCl solutions, however, treatment with L-NAME elevated blood pressure in all animals. Thus NO-induced vasodilation maintains basal arterial blood pressure and limits the pressor response to osmotic stimulation.

Intrajugular infusion (200 microliters/min for 10 min) of 0.85 M NaCl or 1.7 M mannitol in conscious adult male Sprague-Dawley rats increased plasma osmolality similarly and had an additive effect when combined. Plasma Na+ concentration, however, increased with infusion of 0.85 M NaCl, decreased with 1.7 M mannitol, and was not significantly altered by the combined solution. Irrespective of changes in plasma Na+ concentration, plasma vasopressin and oxytocin concentrations were elevated to a similar degree after independent infusion of 0.85 M NaCl or 1.7 M mannitol. With the combined infusion, the change in plasma vasopressin was additive but the change in oxytocin tended to be greater. Accordingly, glucose utilization increased throughout the hypothalamoneurohypophysial system after infusion of 0.85 M NaCl and 1.7 M mannitol. With the combined infusion, however, the change in glucose utilization in the paraventricular nucleus was additive but a synergistic effect occurred in the supraoptic nucleus and neural lobe. Drinking responses were similar in all groups receiving hypertonic solutions, with no additive effect after the combined stimulus. Although our results do not completely rule out the participation of cerebrospinal fluid sodium receptors, it is more likely that osmoreceptors regulate the activity of the hypothalamoneurohypophysial system and drinking behavior. Unlike the magnocellular system, however, drinking behavior seems to be negatively influenced by a stress component of the osmotic stimulation.

I.c.v. administration of a nitric oxide (NO) synthase inhibitor ( N G -monomethyl- l -arginine , NMMA, 500 μg/5 μl) to conscious rats deprived of water for 24 h attenuated drinking and decreased glucose utilization in the subfornical organ and median preoptic nucleus. NMMA did not alter the enhanced glucose utilization in the hypothalamo-neurohypophysial system (HNS) of dehydrated rats, although it has been shown to increase, selectively, oxytocin (OT) secretion [18]. This suggests that NO may act in the neural lobe to inhibit OT secretion and promote the preferential release of vasopressin during dehydration. This effect is similar to the blockade of endogenous opiate receptors by naloxone.

✓ The effect of fetal mesencephalic implants on glucose utilization in selected brain structures and on apomorphine-induced rotational behavior was measured in rats with a unilateral lesion of the substantia nigra. Ipsilateral, but not contralateral, implants decreased the rotational behavior induced by apomorphine. In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula. The increased metabolism in the globus pallidus was attenuated by ipsilateral, but not contralateral, mesencephalic implants which also decreased glucose utilization in the dorsomedial caudate nucleus. These results indicate that the ability of an ipsilateral mesencephalic graft to ameliorate the motor behavior in rats with nigral lesions is associated with changes in the functional activity of the ipsilateral globus pallidus.

Progressive water deprivation increased plasma osmolality, plasma Na+ concentration, and hematocrit in proportion to the severity of dehydration. With increases of 2% in plasma osmolality (24 h dehydration), glucose utilization increased in the supraoptic nuclei and tended to increase in the neural lobe. With further dehydration, glucose utilization also increased in the paraventricular nuclei. These increases were paralleled by depletion of vasopressin and oxytocin contents in the neural lobe and by the enhanced secretion of both hormones into plasma, with a predominant increase of vasopressin. These changes were proportional to the degree of dehydration. With progression of dehydration, decreases in intracellular and extracellular volumes accentuate. Reductions in extracellular volume result in increased angiotensin II (ANG II) formation. Accordingly, glucose utilization in the subfornical organ (SFO), a primary site of ANG II action, increased after 48 and 72 h of dehydration. The median preoptic nucleus, which receives direct inputs from the SFO, also increased glucose utilization at these times. Glucose utilization also increased in the organum vasculosum laminae terminalis, probably in response to the converging inputs from osmoreceptors, volume receptors, and ANG II receptors. Decreases in glucose utilization were observed in the caudal and rostral ventrolateral medulla, perhaps as compensatory responses to decreased extracellular volume to prevent fall in arterial blood pressure.

Topical stimulation of the subfornical organ (SFO) with angiotensin II (ANG II) or acetylcholine (ACh) increased blood pressure, water intake, and the activity of the hypothalamo-neurohypophysial system (HNS). The pressor and drinking responses were higher and the metabolic activity of the HNS, measured with the [14C]deoxyglucose (DG) method, was lower with ANG-II than with ACh. Glucose utilization in the neural lobe increased by 165% with ACh as opposed to 65% with ANG II. These results demonstrate the ANG II and ACh mobilize differentially the mechanisms increasing blood pressure, drinking responses, and the activity of the HNS.

Previous studies have shown that angiotensin II (ANG II) increases glucose utilization in the subfornical organ and stimulates drinking behavior. We investigated with the deoxyglucose method whether atriopeptin III, an atrial natriuretic peptide (ANP), would prevent this enhanced glucose metabolism and interfere with the drinking response in the presence of ANG II. Two rat models with high circulating levels of ANG II were studied: the homozygous Brattleboro and ANG II-infused Sprague-Dawley rats. ANP decreased the normally enhanced glucose utilization in the subfornical organ in the Brattleboro rat and inhibited ANG II-stimulated glucose metabolism in the subfornical organ of Sprague-Dawley rats. This effect was accompanied by decreased ANG II-stimulated water intake. These findings indicate that ANP may act at the level of subfornical organ to antagonize the dipsogenic action of ANG II.

Summary Rates of cerebral glucose utilization were measured by means of the autoradiographic 2-deoxy- d -[14C]glucose technique in 73 normal, awake rats treated with different doses of the α-adrenergic blockers, phenoxybenzamine, phentolamine and yohimbine. Three types of responses were elicited by the administration of these drugs. The predominant effect observed after administration of all α-blockers was a widespread depression of glucose utilization, particularly within the neocortex. The effect was most pronounced with phenoxybenzamine. In a few structures (locus coeruleus, interstitial nucleus of the stria terminalis, medial forebrain bundle, periventricular nucleus and some medullary and hypothalamic nuclei associated with the regulation of blood pressure24) marked increases in glucose utilization were observed. Administration of phentolamine resulted in increased glucose utilization in all the central components of the auditory system (cochlear n., superior olivary n., n. lateral lemniscus, inferior colliculus, medial geniculate body and auditory cortex). Phenoxybenzamine and yohimbine tended to decrease glucose utilization in the auditory system. Alternating columns with higher and lower rates of local glucose consumption were observed in most of the neocortical areas and in the cerebellar vermis. The significance of these columns is not clear.

The autoradiographic 2-[14C]deoxyglucose method was employed to map the distribution of the changes in local cerebral glucose utilization following unilateral and bilateral electrolytic lesions of the lateral habenula nucleus. Local cerebral glucose utilization was measured one week after the placement of the lesions. Unilateral lesions of the nucleus had no effect on the rates of glucose utilization in the 79 brain structures examined. Bilateral lesions, however, produced selective reductions in glucose utilization in several structures compared to the results in sham-operated animals. Reductions were found in the dorsal and median raphe nuclei and the ventral and dorsal tegmental nuclei which receive projecting fibers mainly from the medial part of the lateral habenula nucleus. The rates of glucose metabolism in the interpeduncular nucleus and mamillary body were also reduced by the bilateral habenular lesions. No anatomic structures rostral to the lesions were metabolically affected.

The quantitative autoradiographic deoxyglucose method was used to study changes in local cerebral glucose utilization in conscious dehydrated rats. Animals were either given saline to drink or were deprived of water for 5 days. Saline ingestion did not alter the rates of glucose metabolism in any brain region when compared to the rates of glucose metabolism in animals which had free access to water. Glucose utilization was increased by 140%, however, in the pituitary neural lobe. Water deprivation produced both increases and decreases in glucose metabolism, depending on the particular structure. In 20 of 44 brain structures analyzed, there were significant decreases from −18 to −34% in glucose utilization. Four forebrain structures, the subfornical organ, septal traingular nucleus, and hypothalamic paraventricular and supraoptic nuclei, had increases in glucose utilization of 30–73%. The rate of glucose utilization in the pituitary neural lobe was increased by 37% in water-deprived rats. The results demonstrate that metabolic activity is stimulated in some, but not all, of the structures participating in fluid regulation during an intense thirst challenge. Many brain regions have depressed metabolism in chronic severe dehydration.

The effects of apamin on local rates of glucose utilization in the brain and spinal cord were studied employing the quantitative autoradiographic deoxyglucose method. Forty-five to 60 min after administration of apamin the animals lost exploratory behavior, remaining completely immobile, with the 4 limbs overextended, unresponsive to auditory stimuli. Out of 30 neural structures examined, glucose utilization was significantly decreased in the cochlear n., superior olivary n., lateral lemniscus, inferior colliculus, medial geniculate body, fastigial n., globus pallidus, caudate-putamen, n. accumbens and the lumbar ventral horn of the spinal cord. These results show that apamin specifically affects the functional activity of the auditory and motor structures.

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute adrenalectomy on local cerebral glucose utilization in conscious albino rats. Five hours following removal of the adrenal glands, glucose utilization was increased (4-55%) throughout the brain, particularly in the locus ceruleus, hypothalamic paraventricular nucleus, hippocampus, median eminence and anterior lobe of the pituitary gland. These structures are involved in the regulation of corticotropin-releasing factor, vasopressin, and adrenocorticotropic hormone. Treatment with dexamethasone (0.25 mg/kg i.m.) substantially reduced or prevented the stimulatory effects of adrenalectomy on cerebral glucose metabolism. These results demonstrate: (1) the existence of a negative feedback loop between the brain and adrenal glands in which corticosteroids exert an inhibitory action on glucose utilization of brain regions participating in adrenotropic regulation, and (2) a general inhibitory action of glucocorticoids on cerebral metabolism.

Homozygous Brattleboro rats have a genetic inability to synthesize vasopressin and therefore manifest the signs and symptoms of diabetes insipidus. Measurement of local cerebral glucose utilization in these rats has revealed increases specifically localized to the subfornical organ and pituitary neural lobe. Vasopressin replacement reverses the increased glucose utilization only in the subfornical organ. The results suggest that vasopressin regulates the rate of glucose metabolism in the subfornical organ.

Angiotensin II infused intravenously into sinoaortic-denervated rats induced drinking and increased glucose utilization in the subfornical organ and pituitary neural lobe in amounts not different from those observed in sham-operated animals. We suggest that inputs from baroreceptors have a negligible influence on glucose metabolism in the subfornical organ during infusion of angiotensin II.

We review results from several rat models of dehydration in which increases in the rate of glucose utilization were found in the subfornical organ and in other cerebral structures participating in the regulation of thirst and fluid balance. During chronic saline ingestion, the simplest model of dehydration involving only plasma hypertonicity, glucose utilization in the subfornical organ was normal. In water-sated homozygous Brattleboro rats, in which plasma osmolality and levels of angiotensin II are increased, glucose metabolism in the subfornical organ was 44% higher than in water-sated Long-Evans rats. In a complex model of dehydration, chronic water deprivation which is associated with high levels of plasma osmolality, angiotensin II, and baroreceptor disinhibition, there was a 72% increase in subfornical organ glucose utilization. The results suggest that angiotensin II is an important stimulant of metabolism in the subfornical organ, and that converging stimuli have a synergistic effect on metabolic activity in this structure.

Electrical stimulation of the proximal stump of the transected sciatic nerve increased glucose utilization in the ventral horn of the spinal cord, with the greater increase in Rexed's lamina IX. Antidromic stimulation of the ventral root, however, did not change glucose utilization in the ventral horn. These results suggest that the axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased electrical activity in these elements.

The quantitative autoradiographic 2-[14C]deoxyglucose method was employed to map the metabolic activity of the superior cervical ganglion and the entire brain during unilateral electrical stimulation of the cervical sympathetic trunk in the urethane-anesthetized rat. Stimulation of the cervical sympathetic trunk increased glucose utilization in the ipsilateral superior cervical ganglion (+95%) but did not produce side-to-side differences in glucose utilization in any of the brain structures examined in this study. Compared to the control nonstimulated animals, the rate of glucose metabolism in the pineal gland was increased 71% following stimulation of the cervical sympathetic trunk. The pineal gland was the only brain region out of 87 structures examined in which glucose utilization was increased by electrical stimulation of its sympathetic innervation.

Brainstem auditory evoked potentials (BAEPs) were recorded from rats before and after injection with apamin, a polypeptide component of bee venom. Increased absolute and interpeak latencies were found in Peaks III-VII of the BAEP beginning about 30 minutes after apamin injection suggesting impaired auditory function. No change in BAEP was found when animals were injected with saline or during the baseline period before apamin administration. Results corroborate recent findings from our laboratories of decreased glucose metabolism in brainstem nuclei of the auditory system [3] after injection with the same dose of apamin.

Local rates of glucose utilization in the superior cervical, cardiac, and coeliac ganglia were measured by means of the autoradiographic 2-deoxy-d-[14C]glucose method in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), 32–34, 46–48, and 78–87 days old. Brain glucose utilization was examined in 78–87-day-old SHR and WKY. At 32–34 days (at which time mean arterial blood pressure was normal and similar in both groups of rats), the rates of glucose utilization of all three sympathetic ganglia were the same in both groups. At 46–48 days, despite the fact that blood pressure had risen significantly in SHR (mean ± SEM, 136 ± 3 mm Hg, n = 5, compared to 113 ± 3 mm Hg, n = 5, in the control WKY), glucose utilization was decreased in the cardiac and coeliac ganglia but not in the superior cervical ganglia of the SHR. At 78–87 days, glucose utilization was reduced in all the sympathetic ganglia of the hypertensive rats. These results suggest that the sympathetic system is less active in SHR and indicate that hyperactivity of the sympathetic nervous system is not part of the mechanism of the hypertension. Of 44 structures examined in the central nervous system, only the external cuneate, vestibular, and fastigial nuclei of the SHR exhibited increased rates of glucose utilization, and no changes were found in any of the other structures. These increases are probably not related to the origin or maintenance of the hypertension, inasmuch as lesioning of the vestibular or fastigial nuclei did not decrease blood pressure in the SHR.

The subfornical organ is a major receptor area for one of the principal stimuli of thirst, the octapeptide, angiotensin II. In conscious water-sated rats, we examined the effects of intravenous infusion of angiotensin II on the rat of glucose utilization in the subfornical organ and in structures anatomically and functionally connected with it. Angiotensin II produced pressor and drinking responses and increased glucose utilization selectively in the subfornical organ and pituitary neural lobe and in no other brain structure. Treatment with the angiotensin II antagonist, sar 1 -leu 8 -angiotensin II, before intravenous administration of angiotensin II prevented metabolic stimulation of the subfornical organ and neural lobe. Captopril, an inhibitor of angiotensin-converting enzyme, was administered to homozygous Brattleboro rats, which normally have elevated rates of glucose utilization in the subfornical organ. Captopril reduced subfornical organ glucose metabolism to a level similar to that found in control animals. These results demonstrate that peripheral angiotensin II stimulates glucose metabolism in the subfornical organ under conditions in which it provokes drinking and pressor responses. The findings suggest that circulating angiotensin II is responsible for the high rat of glucose utilization observed in the subfornical organ of Brattleboro rats homozygous for diabetes insipidus.

1. The central structures responsible for the gastrosecretory effect of cytoglucopoenia caused by 2-deoxy-D-glucose (2-DG) were investigated in 105 cats prepared with chronic gastric fistulae and subjected to various experimental procedures. 2. Bilateral electrolytic lesion of the caudalmost two thirds of globus pallidus almost suppressed the secretory response and caused aphagia and adipsia. 3. Secretion in response to 2-DG and feeding behaviour were entirely blocked after making a lesion in a large ventromedial area of the meso diencephalic transition comprising the ventral tegmental area of Tsai, the ventral tegmental decussation, the red nucleus, a ventral portion of the central grey matter, the interstitial nuclei of Darkschewitsch and of Cajal, the pre-rubral fields, the reticular part of substantia nigra, the internal portion of the cerebral peduncle and the ventral part of the mesencephalic reticular formation. 4. Microinjection of 2-DG in the medial forebrain bundle, at the level of the hypothalamus, caused intense gastric secretion, whereas the same procedure was totally ineffective when the caudalmost two thirds of the globus pallidus were stimulated. 5. Increasing doses of 2-DG, systemically injected, restored the secretory response in volume and acid concentration and output after intercollicular transection of the brain stem. After the transection, secretion of pepsin was only slightly increased when large doses of 2-DG were administered, thus suggesting a differential control of water, acid and pepsin secretion in response to cytoglucopoenia. 6. It is concluded that there are at least three reflex systems involved in gastric secretion due to cytoglucopoenia: (a) a reflex consisting of afferent and efferent pathways in the medial forebrain bundle area; (b) a reflex whose afferent side is from the hypothalamus and efferent side is from the globus pallidus; (c) a reflex with the afferent side probably originating in the liver and the efferent side in the lower brain stem. 7. The pathways involved in the first two arcs run along Nauta's limbic mid-brain circuit. The three systems are possibly related to control of secretion and feeding behaviour.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

Electrical stimulation of the proximal stump of the transected sciatic nerve produces a frequency-dependent activation of glucose utilization, measured with the autoradiographic deoxy [14C]glucose method, in the dorsal horn of the spinal cord but produces no change in glucose utilization in the dorsal root ganglion cells. These results suggest that axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased functional activity of this pathway.

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute dehydration on local cerebral glucose utilization in Long-Evans and homozygous Brattleboro rats. Water-sated Brattleboro rats had high rates of glucose utilization in the subfornical organ, habenular complex, septal triangular nucleus and pituitary neural lobe. Deprivation of water for 16–18 h enhanced glucose utilization in these structures, more intensely in the Brattleboro rats, and activated others, particularly those connected to the subfornical organ. In Long-Evans rats, water deprivation increased metabolic activity in the subfornical organ, in several structures with which it is connected, and in other brain regions putatively involved in maintaining fluid balance.

The autoradiographic deoxyglucose method was employed to investigate: 1) whether the increased glucose utilization in the subfornical organ (SFO) during administration of angiotensin II (AII) depends on the neural inputs to the SFO; and 2) to investigate whether the activation of the hypothalamo-neurohypophysial system during administration of AII depends on inputs from the SFO. The ventral stalk of the SFO, which contains the majority of efferent and afferent projections of this circumventricular structure, was interrupted with knife cuts three days before the deoxyglucose experiments. Intravenous infusion of AII (2.5 μg/min) for 45 min increased glucose utilization in the SFO and neural lobe in the lesioned animals to the same extent as in the sham-operated animals. Drinking, however, was significantly reduced in lesioned animals. These experiments disclose independent parallel mechanisms responsible for activation of the SFO and the hypothalamo-neurohypophysial system by AII.

Receptor densities for angiotensin II and atriopeptin are particularly high in the dorsal vagal complex (DVC) of the caudal medulla oblongata. Measurements of glucose metabolism in individual components of the DVC, compared with those in Long-Evans rats, revealed that the area postrema was activated selectively both in water-sated and water-deprived Brattleboro rats, which have high circulating levels of angiotensin II. Other parts of the DVC, including subnuclei of the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve, as well as brainstem structures within efferent trajections of the DVC, had elevated rates of glucose metabolism in Brattleboro rats deprived of water overnight and in Sprague-Dawley rats dehydrated for 120 h. The findings are consistent with neural activation by angiotensin II, as either a hormone or neurotransmitter, within subregions of the dorsal medulla oblongata having high densities of putative receptors and immunoreactive perikarya and fibers containing both angiotensin II and atriopeptin.

✓ Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent.