Altered NaCl taste responses precede increased NaCl ingestion during Na(+) deprivation.

It has been suggested that Na(+) deficiency alters the sensitivity of taste receptors, thereby rendering NaCl solutions more palatable or preferred and more likely to be ingested. Increased ingestion of concentrated NaCl solutions by rats during dietary Na(+) deprivation occurs only after approximately 8-10 days. To determine whether changes in gustatory responses mediate the deprivation-induced NaCl ingestion (salt appetite), we evaluated taste responses to a range of NaCl concentrations before, during, and after dietary Na(+) deprivation. Rats were trained to lick rapidly in short-duration (10 s) tests by mixing NaCl solutions in a dilute sucrose solution. This method elicited consistent, interpretable rates of licking, even of normally avoided NaCl concentrations, without the necessity of depriving the rats of water. The licking rate increased after dietary Na(+) deprivation of only 2 days, increased further after 5 days of Na(+) deprivation and, after 10 days, was not different from that after 2 days. These results suggest that a change in the response to NaCl taste, as evidenced by increased rates of licking during short-access tests, occurred after 2 days of dietary Na(+) deprivation. In contrast, a significant increase in the 24-h ingestion of a concentrated NaCl solution occurred only after approximately 1 week of maintenance on Na(+)-deficient chow. Thus, it is unlikely that a delayed change in the response to NaCl taste to more palatable or preferred underlies the delayed increase in 24-h NaCl intake during dietary Na(+) deprivation.

Osmoregulation in water-deprived rats drinking hypertonic saline: effect of area postrema lesions.

Rats drank rapidly when 0.3 M NaCl was the only drinking fluid available after overnight water deprivation, consuming approximately 200 ml/24 h. Although such large intakes of this hypertonic solution initially elevated plasma osmolality, excretion of comparable volumes of urine more concentrated than 300 meq Na(+)/l ultimately appears to restore plasma osmolality to normal levels. Rats drank approximately 100 ml of 0.5 M NaCl after overnight water deprivation, but urine Na(+) concentration (U(Na)) did not increase sufficiently to achieve osmoregulation. When an injected salt load exacerbated the initial dehydration caused by water deprivation, rats increased U(Na) to void the injected load and did not significantly alter 24-h intake of 0.3 or 0.5 M NaCl. Rats with lesions of area postrema had much higher saline intakes and lower U(Na) than did intact control rats; nonetheless, they appeared to osmoregulate well while drinking 0.3 M NaCl but not while drinking 0.5 M NaCl. Detailed analyses of drinking behavior by intact rats suggest that individual bouts were terminated by some rapid postabsorptive consequence of the ingested NaCl load that inhibited further NaCl intake, not by a fixed intake volume or number of licks that temporarily satiated thirst.

Area postrema and sympathetic nervous system effects of vasopressin and angiotensin II.

1. Precise control over the cardiovascular system requires the integration of both neural and humoral signals related to blood volume and blood pressure. Humoral signals interact with neural systems, modulating their control over the efferent mechanisms that ultimately determine the level of pressure and volume. 2. Peptide hormones such as angiotensin (Ang)II and arginine vasopressin (AVP) act through circumventricular organs (CVO) to influence cardiovascular regulation. 3. The area postrema (AP), a CVO in the brainstem, mediates at least some of the central actions of these peptides. Vasopressin appears to act in the AP to cause sympathoinhibition and a shift in baroreflex control of the sympathetic nervous system (SNS) to lower pressures. These effects of AVP and the AP appear to be mediated by alpha2-adrenoceptor and glutamatergic mechanisms in the nucleus tractus solitarius. 4. In contrast to AVP AngII has effects in the AP to blunt baroreflex control of heart rate and cause sympathoexcitation. The effects of chronic AngII to increase activity of the SNS may be due to AP-dependent activation of neurons in the rostral ventrolateral medulla.

High dietary NaCl early in development enhances mean arterial pressure of adult rats.

We investigated the long-term influence of early dietary NaCl on adult mean arterial pressure (MAP) and heart rate (HR), assessed continuously for 7 weeks when fed water and chow containing 1% NaCl (weeks 1, 4, 7), 0% NaCl (weeks 2-3), and 3% NaCl (weeks 5-6) while on a 12:12 light/dark cycle. Subjects were offspring of female Sprague-Dawley rats fed solid chow consisting of either 0.1% (basal), 1% (intermediate), or 3% (high) NaCl throughout pregnancy and lactation. After weaning on postnatal day (PD) 21, offspring were fed the same NaCl diet of their mother until PD 30, at which time all offspring were given Purina 5001 diet (1% NaCl) as their solid chow. On PD 60, 22 adult male offspring (eight basals, six intermediates, eight highs) were implanted with an aortic electronic sensor for transmitting blood-pressure signals by telemetry. MAP and HR varied significantly across the 7-week testing period in association with dietary NaCl levels. The three perinatal salt groups had similar HR levels on normal 1% NaCl chow. However, HR increased in all groups during 0% NaCl and decreased in all groups during 3% NaCl. In contrast, the average MAP levels were significantly greater in the highs compared to both the intermediate and basal groups during both dark and light periods. MAP increased in high and basal groups during both 0% and 3%; however, the increase was more pronounced in the highs. In conclusion, exposure to high levels of dietary NaCl early in development led to a persistent increase in MAP in adulthood.

Fos expression in brain stem nuclei of pregnant rats after hydralazine-induced hypotension.

Fos and dopamine beta-hydroxylase immunoreactivity were evaluated in the brain stems of 21-day pregnant and virgin female rats injected with either hydralazine (HDZ; 10 mg/kg iv) or vehicle. HDZ produced significant hypotension in both groups, although baseline blood pressure was lower in pregnant rats (96 +/- 2.5 mmHg) than in virgin female rats (121 +/- 2.8 mmHg). There were no differences in Fos immunoreactivity in the brain stems of pregnant and virgin female rats after vehicle treatment. HDZ-induced hypotension significantly increased Fos expression in both groups; however, the magnitude of the increases differed in the caudal ventrolateral medulla (CVL), the area postrema (AP), and the rostral ventrolateral medulla (RVL). Fos expression after HDZ in pregnant rats was augmented in noncatecholaminergic neurons of the CVL but was attenuated in the AP and in noncatecholaminergic neurons in the RVL. These results are consistent with differences in the sympathetic response to hypotension between pregnant and virgin female rats and indicate that the central response to hypotension may be different in pregnant rats.

Impaired osmoregulatory responses in rats with area postrema lesions.

Area postrema lesions (APX) in adult male rats produced a robust spontaneous intake of 0.5 M NaCl, as reported previously. The largest NaCl intakes (up to 108 ml/day) were observed when there was little incidental damage in the medial subnucleus of the nucleus of the solitary tract adjacent to the caudal and middle portions of the area postrema. Rats with discrete APX also drank substantial amounts of 0.5 M NaCl when access to saline was restricted to 7 h/day (up to 30 ml in 1 h, 48 ml in 7 h). Such large NaCl intakes stimulated considerable water ingestion and renal sodium excretion, but together these responses usually were insufficient for osmoregulation during the 7-h test period. After systemic administration of hypertonic NaCl solution, rats with APX excreted less Na(+) in urine and secreted less vasopressin and oxytocin than control rats did. The prominent salt appetite, insufficient thirst and natriuresis in response to an ingested NaCl load, and blunted natriuresis and neurohypophysial hormone secretion in response to an injected NaCl load, all indicate that osmoregulatory responses are impaired in rats after APX.

Fos expression following isotonic volume expansion of the unanesthetized male rat.

Cardiopulmonary afferents, baroreceptor afferents, or atrial natriuretic peptide binding to circumventricular organs may mediate the central response to volume expansion, a condition common to pregnancy, exercise training, and congestive heart failure. This study used Fos immunocytochemistry to examine brain regions activated by volume expansion. Male Sprague-Dawley rats were infused with isotonic saline equal to 10% of their body weight in 10 min followed by a maintenance infusion of 0.5 ml/min for 110 min. Control animals received 2-h infusions at 0.01 ml/min. Five minutes after the start of volume expansion, central venous pressure of expanded animals was significantly greater than control animals. The volume-expanded group exhibited significantly greater Fos activation (P < 0.05) in the area postrema, nucleus of the solitary tract, caudal ventrolateral medulla, paraventricular nucleus, supraoptic nucleus, and perinuclear zone of the supraoptic nucleus. Double labeling indicates that oxytocinergic neurons in the supraoptic nucleus are activated. Neurons in brain regions known to inhibit both sympathetic activity and vasopressin release show increased Fos expression following isotonic volume expansion.

Rats with area postrema lesions have lengthy eating and drinking bouts when fed ad libitum: implications for feedback inhibition of ingestive behavior.

Ad libitum ingestive behavior of rats with area postrema lesions (APX) was monitored electronically every 6 s for 23 hr. Whereas control rats ate on average 32.2 g of food each day in 16.3 distinct bouts, rats with APX ate comparable amounts of food (28.6 g) in much fewer daily bouts (5.8) that were very large. Controls drank 38.4 ml of water daily in 17.8 bouts, whereas rats with APX consumed more than twice as much water (101.5 ml) in a similar number of bouts (18.5). Controls drank 5.3 ml of 0.5 M NaCl daily in 7.0 bouts, whereas rats with APX consumed 9 times as much saline (45.5 ml) in more bouts (18.2) that were relatively large. These and other results suggest that the area postrema plays an important role in detecting inhibitory signals generated by food or fluid intake and that feeding and drinking bouts may increase in size after APX, because the feedback inhibition provided by those signals is diminished.

Enhanced fluid intake by rats after capsaicin treatment.

These studies examined stimulated fluid intake by rats in which vagally mediated signals of gastric distension were blunted by systemic treatment with the neurotoxin capsaicin, as verified by the loss of cholecystokinin-induced inhibition of feeding. After overnight food deprivation, intake of a 10% sucrose solution by capsaicin-treated rats was greater than that by control rats. Similarly, capsaicin-treated rats drank more water than did control rats when stimulated by plasma hyperosmolality after intraperitoneal administration of hypertonic NaCl or by isosmotic hypovolemia after subcutaneous administration of a hyperoncotic colloidal solution. Finally, during chronic administration of the mineralocorticoid deoxycorticosterone acetate, capsaicin-treated rats consumed more concentrated saline than did control rats. In all tests, intakes by capsaicin-treated rats were significantly greater than those by control rats within 5-15 min. These results suggest that early signals of gastric distension, such as those that occur during normal episodes of food, water, or NaCl intake, may modulate ongoing ingestion and that, with the attenuation of such general inhibitory signals, ingestion continues until gastric distension becomes larger and/or later postgastric signals are detected.

Area postrema lesions in rats appear to disrupt rapid feedback inhibition of fluid intake.

Area postrema lesions (APX) were produced by vacuum aspiration in adult male rats. After systemic administration of hypertonic saline solutions, significantly more water was consumed by rats with APX than by intact control rats. Similarly enhanced water intake by rats with APX also was observed when marked hypovolemia was induced by s.c. administration of a hyperoncotic colloidal solution. In both conditions, the increased water intake occurred within the first 15 min of the drinking tests. Intakes of liquid diet or 10% sucrose solution after food deprivation by rats with APX also were considerably larger than those of control rats. These and other results suggest that rats with APX experience less inhibition of ingestion while drinking. Thus, the AP may be important for the detection of early, inhibitory signals generated by fluid ingestion, and after its ablation increased drinking may occur because the feedback inhibition provided by such signals is diminished.

Dehydration anorexia in decerebrate rats.

Hypertonic saline (HS) administered intraperitoneally reduced the intake of sucrose solution infused intraorally in tube-fed decerebrate rats, as it did in control animals. Similarly, either intraperitoneal or intravenous HS markedly decreased the intake of laboratory chow by neurologically intact control rats. These observations complement recent findings that lesions of putative osmoreceptors in the ventral diencephalon, which eliminate thirst and blunt pituitary secretion of vasopressin and oxytocin in response to HS in rats, have no apparent effect on the HS-induced inhibition of food intake. Taken together they support previous studies indicating an important role for the caudal brainstem in the central control of food intake and suggest that such brainstem control may also include the inhibition of food intake induced by acute hyperosmolality.

Lithium chloride-induced anorexia, but not conditioned taste aversions, in rats with area postrema lesions.

Area postrema (AP) lesions were produced by vacuum aspiration in adult male Sprague-Dawley rats. Consistent with previous findings, when water-deprived rats were allowed to drink novel flavored fluids immediately before treatment with LiCl (3 mEq/kg, i.p.), sham-operated and non-operated control rats demonstrated a pronounced aversion to the fluids whereas rats with AP lesions did not decrease fluid consumption significantly. However, in a 30-min test period after overnight food deprivation, rats with AP lesions reduced food intake significantly and to an equivalent degree as control animals when pretreated with LiCl (3 mEq/kg, i.p. or i.v.). These and other results are consistent with the traditional view that AP mediates the sensation of nausea produced by LiCl treatment (hence the loss of conditioned taste aversions after AP lesions), but suggest that neither nausea nor AP is necessary for the marked disinclination to eat that is induced in rats by acute administration of LiCl.

Evaluation of granulocytic ehrlichiosis in dogs of Missouri, including serologic status to Ehrlichia canis, Ehrlichia equi and Borrelia burgdorferi.

Canine granulocytic ehrlichiosis was diagnosed in 37 dogs by finding ehrlichial morulae in 0.1 to 26.2% of their blood neutrophils and eosinophils. All 37 dogs had clinical signs of arthritis or muscular stiffness. Titer to Ehrlichia canis was determined in sera from 31 of the 37 dogs; 25 dogs had titer ranging from 1:20 to 1:5,120. In the other 6 dogs, titer to E canis was less than 1:10. The most common hematologic abnormality in these dogs, other than rickettsiemia, was thrombocytopenia. Granulocytes infected with ehrlichial organisms were not found in another 10 dogs that had clinical signs of arthritis or muscular stiffness. Of these 10 dogs, 3 had titer to E canis ranging from 1:40 to 1:320. Titer in the other 7 dogs was less than 1:10. Ehrlichial morulae were not found in the granulocytes of 18 healthy dogs. Of these 18 dogs, 9 had titer to E canis ranging from 1:20 to 1:5,120. Titer in the other 9 dogs was less than 1:10 Titer to Borrelia burgdorferi was determined in dogs with granulocytic ehrlichiosis, arthritic dogs without detected rickettsiemia, and in healthy dogs. Low titer determined by 2 laboratories was considered to be nonspecific reaction in all 3 groups of dogs and, thus, did not indicate that the arthritic disorders were attributable to canine borreliosis.

Experimental transmission of granulocytic ehrlichial organisms in dogs.

Canine granulocytic ehrlichial organisms were transmitted from an infected dog from Missouri to two male, 10-month-old dogs by an intravenous injection of whole blood. Physical or behavioral abnormalities were not detected during the 98 days of evaluation other than a mild pyrexia from Day 18 to 20. Ehrlichial morulae were found in blood granulocytes of Dog 1 from Day 13 to 44 and of Dog 2 from Day 14 to 34 with the peak rickettsemia occurring on Day 16 for both dogs. By Day 21 after inoculaiuon, both dogs had positive titers to Ehrlichia canis. The highest titers for both dogs were found 63 days after inoculation, after which the titers decreased. Most of the hematologic abnormalities (i.e., neutropenia, lymphocytosis, thrombocytopenia) and fever occurred between 18 and 24 days after inoculation. The pathologic bases of these abnormalities were not investigated but their concurrent presence suggested an association with the dogs' immunologic responses to the granulocytic ehrlichial agent. Results from the study indicated that the canine granulocytic ehrlichial agent of Missouri may produce subclinical infections and suggested that dogs may be able to clear the organism without antimicrobial therapy.