Decreased Water Intake Research Articles

Angiotensin-(1-7) serves as an aquaretic by increasing water intake and diuresis in association with downregulation of aquaporin-1 during pregnancy in rats

We previously demonstrated that kidney and urine levels of angiotensin-(1-7) [ANG-(1-7)] were increased in pregnancy. To explore the role of ANG-(1-7) on fluid and electrolyte homeostasis during pregnancy, we evaluated the effect of the ANG-(1-7) antagonist D-alanine-[ANG-(1-7)] (A-779) on kidney function. Virgin and pregnant rats received infusion of vehicle or A-779 (48 microg.kg(-1).h(-1)) for 8 days by osmotic minipumps. Metabolic studies were done on treatment day 7-8. Virgin and pregnant rats at day 15 and 19 were killed, and blood and kidneys were collected. Kidneys were prepared for Western blot analysis for aquaporin-1 (AQP1) and aquaporin-2. In virgin female rats, A-779 increased urine volume and decreased urinary osmolality and AQP1 with no change in water intake. In 19-day pregnant rats, A-779 significantly decreased water intake and urine volume and increased urinary osmolality and kidney AQP1 expression. Only in late gestation did A-779 treatment decrease the difference between intake and output (balance). A-779 treatment increased plasma vasopressin in late gestation but did not change vasopressin in virgins. In virgin and pregnant animals, A-779 administration had no effect on blood pressure, plasma volume, blood volume, or urinary electrolytes. These results suggest that ANG-(1-7) produces antidiuresis associated with upregulation of AQP1 in virgin rats, whereas ANG-(1-7) produces diuresis in late gestation with downregulation of AQP1. ANG-(1-7) contributes to the enhanced water intake during pregnancy, allowing maintenance of the normal volume-expanded state despite diuresis produced in part by decreased AVP and AQP1.

The effect of dextromethorphan in preventing cholecalciferol‐induced poison shyness and sickness‐induced anorexia in the laboratory Norway rat

Overcoming bait and poison shyness is critical to the success of pest control operations against rats and other rodents. The authors hypothesized that the N-methyl-D-aspartate receptor blocker, dextromethorphan, could prevent the acquired memory of sickness and sickness-induced anorexia resulting from rodents eating poisoned bait. Cholecalciferol (1/4 LD(50)) was mixed with dextromethorphan and fed to rats on two 2 day sessions, with an 18 day break in between. Dextromethorphan did not prevent poison shyness; during the second poisoning period, both the cholecalciferol only and the cholecalciferol plus dextromethorphan groups had lower intakes of the bait compared with the control and dextromethorphan only groups. In addition to the previously recorded symptoms of cholecalciferol poisoning, the rats in this trial were observed to have nose bleeds, weepy eyes, laboured breathing and, in the case of the cholecalciferol only treated group, a period of decreased water intake followed by a period of increased water intake. There was also a period of increased water intake in the cholecalciferol plus dextromethorphan group. Dextromethorphan failed to prevent poison shyness and the anorectic effect of cholecalciferol. However, it did reduce anorexia from 17 days in the cholecaliferol group to 8 days in the cholecalciferol plus dextromethorphan group.

Blood Volume Response to Physical Activity and Inactivity

Data from both cross-sectional and longitudinal studies provide compelling evidence that circulating blood volume can be influenced by regular physical activity or inactivity. Expansion or contraction of plasma volume can account for most of the alteration in circulating blood volume during the initial 1 to 2 weeks of changing physical activity patterns; after this time, altered blood volume may be distributed equally between plasma and red cell volumes. Alterations in circulating blood volume that accompany changes in physical activity represent a net change in total body water and solutes that are associated with increased or decreased water intake and urine volume and solute output. The mechanism of altered urine output appears to be a modified renal tubular reabsorption of sodium. The expansion of blood volume that accompanies physical activity provides advantages of greater body fluid for heat dissipation (sweating) and thermoregulatory stability as well as larger vascular volume for greater cardiac filling and stroke volume and cardiovascular stability during exercise and orthostatic challenges. The opposite is true when blood volume is reduced during periods of relative physical inactivity. The observation that underlying mechanisms for alteration in blood volume with physical activity and inactivity are similar but respond directly opposite suggests that they are intricately related. These relations have implications as to a mechanism by which physical activity and fitness may be protective against reduced blood volume and subsequent development of cardiovascular disease associated with aging.

Local production of angiotensin II in the subfornical organ causes elevated drinking

The mechanism controlling cell-specific Ang II production in the brain remains unclear despite evidence supporting neuron-specific renin and glial- and neuronal-specific angiotensinogen (AGT) expression. We generated double-transgenic mice expressing human renin (hREN) from a neuron-specific promoter and human AGT (hAGT) from its own promoter (SRA mice) to emulate this expression. SRA mice exhibited an increase in water and salt intake and urinary volume, which were significantly reduced after chronic intracerebroventricular delivery of losartan. Ang II-like immunoreactivity was markedly increased in the subfornical organ (SFO). To further evaluate the physiological importance of de novo Ang II production specifically in the SFO, we utilized a transgenic mouse model expressing a floxed version of hAGT (hAGT(flox)), so that deletions could be induced with Cre recombinase. We targeted SFO-specific ablation of hAGT(flox) by microinjection of an adenovirus encoding Cre recombinase (AdCre). SRA(flox) mice exhibited a marked increase in drinking at baseline and a significant decrease in water intake after administration of AdCre/adenovirus encoding enhanced GFP (AdCre/AdEGFP), but not after administration of AdEGFP alone. This decrease only occurred when Cre recombinase correctly targeted the SFO and correlated with a loss of hAGT and angiotensin peptide immunostaining in the SFO. These data provide strong genetic evidence implicating de novo synthesis of Ang II in the SFO as an integral player in fluid homeostasis.

The antinociceptive efficacy of buprenorphine administered through the drinking water of rats

Postoperative pain management in laboratory animals is important for animal welfare and required under law in many countries. Frequent injection of analgesics to rodents after surgery is stressful for the animals and labour-intensive for animal care personnel. An alternative dosing scheme such as administration of analgesics in the drinking water would be desirable. However, the efficacy of a chronic oral analgesic treatment via this route has not yet been documented. This study investigated the antinociceptive efficacy of buprenorphine administered ad libitum via the drinking water of laboratory rats. The antinociceptive efficacy of buprenorphine in drinking water was compared with repeated subcutaneous injections. A comparison was also made between buprenorphine in drinking water and the combination of one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water. Antinociception was assessed by use of an analgesiometric model measuring the rats' latency time to withdrawal from a noxious heat stimulus applied to the plantar surface of the paw. Results revealed that buprenorphine in drinking water (0.056 mg/mL) induced significant increases in paw withdrawal latency times during a three-day period of administration with a maximal effect at 39 h after the start of buprenorphine administration. One single injection of buprenorphine (0.1 mg/kg s.c.) followed by buprenorphine in the drinking water (0.056 mg/mL) induced an earlier onset of antinociception than buprenorphine in drinking water alone. In contrast, buprenorphine (0.1 mg/kg s.c.) injected every 8 h over a period of three days did not result in significant increases in paw withdrawal latency times. In conclusion, our results suggest that one single subcutaneous injection of buprenorphine followed by buprenorphine in drinking water may be a viable treatment option for the relief of pain in laboratory rats, but at the doses used in this study in pain-free rats it was associated with a decrease in water intake and some behavioural changes.

Angiotensin‐(1–7) increases water intake and produces diuresis in association with down‐regulation of aquaporin‐1 during pregnancy in rats

Previous studies showed that kidney and urine levels of angiotensin-(1–7) [Ang-(1–7)] were increased in pregnancy (PR). Since the role of Ang-(1–7) on fluid and electrolyte homeostasis during PR has not been explored, we evaluated the effect of the Ang-(1–7) antagonist A-779 on kidney function. Virgin and PR rats at gestational day 7 and 11 received infusion of vehicle or Ang-(1–7) antagonist A-779 (48μg/kg/hr) for 8 days by osmotic minipumps. Metabolic studies were completed on treatment day 7–8. Virgin and PR at day 15 and 19 were sacrificed and kidneys were prepared for western blot analysis using polyclonal antibodies for AQP1 and AQP2. Urine volume increased progressively throughout gestation in vehicle, but not in A-779 treated rats. In 19d-PR rats, A-779 as compared to vehicle significantly decreased urine volume (19 ± 2 vs 28 ± 2 mL/24hr, p<0.05), increased urinary osmolality (1038 ± 80 vs 844 ± 66 mOsm/L, p<0.05), and decreased water intake (37 ± 3 vs 53 ± 3 ml/24hr, p<0.05), but had no effect on urinary sodium and potassium excretion. AQP1 kidney expression (28kDa) (15 ± 6 vs 4 ± 1 ROD, p<0.05) was significantly increased in A-779 treated 19d-PR rats without a change in AQ2 (29kDa). These studies suggest that Ang-(1–7) increases water intake and produces diuresis during late pregnancy by decreasing water reabsorption through down-regulation of the kidney AQP1 water channel. Sponsored by HL051952; AHA0615416

White bean amylase inhibitor administered orally reduces glycaemia in type 2 diabetic rats.

A purified pancreatic alpha-amylase inhibitor (alpha-AI) from white beans (Phaseolus vulgaris) was administered orally (100 mg/kg body weight dissolved in 9 g NaCl/l) for 22 d to non-diabetic (ND) and type 2 diabetic (neonatal diabetes models n0-STZ and n5-STZ) male Wistar rats. Mean glycaemia (mmol/l) declined from day 4 of the alpha-AI administration in ND rats (5.48 (sem 0.08) v. 4.39 (sem 0.13); P<0.05), n0-STZ diabetic rats (7.94 (sem 0.42) v. 5.56 (sem 0.32); P<0.01) and n5-STZ diabetic rats (17.34 (sem 2.58) v. 11.93 (sem 1.96)), until the end of treatment: ND (5.22 (sem 0.21) v. 3.97 (sem 0.06); P<0.01); n0-STZ (8.10 (sem 0.19) v. 5.21 (sem 0.30); P<0.01); and n5-STZ (16.36 (sem 2.14) v. 7.69 (sem 1.34); P<0.01). There was a decrease in water intake (ml/d) in the alpha-AI-treated diabetic rats: n0-STZ (30 (sem 0.10) v. 22 (sem 1.50); P<0.01) and n5-STZ (76 (sem 5.04) v. 57 (sem 4.85); P<0.01). Food intake (g/d) decreased in all three groups: ND (23 (sem 0.31) v. 20 (sem 0.03); P<0.05); n0-STZ (22 (sem 0.55) v. 16 (sem 0.98); P<0.01); and n5-STZ (31 (sem 0.58) v. 23 (sem 1.20); P<0.01). The enterocyte sucrase and maltase activities (U/g proteins) were high (P<0.01) in the untreated diabetic rats, n0-STZ (45 (sem 4) and 152 (sem 10), respectively) and n5-STZ (67 (sem 12) and 151 (sem 10), respectively) with respect to the ND rats (24 (sem 2) and 74 (sem 10), respectively). After alpha-AI treatment, enzyme activities declined in both diabetic rats, n0-STZ (21 (sem 2) and 85 (sem 11); P<0.01) and n5-STZ (28 (sem 7) and 75 (sem 19); P<0.05), to values close to those in the ND rats. In conclusion, alpha-AI significantly reduced glycaemia in both the ND and diabetic animals and reduced the intake of food and water, and normalized the elevated disaccharidase levels of the diabetic rats.

Involvement of central H 1 and H 2 receptors in water intake induced by hyperosmolarity, hypovolemia and central cholinergic stimulation

In the present study we investigated the participation of central H 1 and H 2 histaminergic receptors in water intake induced by hyperosmolarity (evoked by intragastric salt load), by hypovolemia (promoted by the subcutaneous administration of polyethyleneglycol) and by the pharmacological stimulation of central cholinergic pathways by the muscarinic agonist carbachol in male Wistar rats. The data presented here show that the pharmacological blockade of central H 1 histaminergic receptors by third ventricle injections of mepyramine significantly decreased water intake induced by hyperosmolarity, hypovolemia and by the intracerebroventricular injections of carbachol. On the other hand, the pharmacological blockade of central H 2 histaminergic receptors by third ventricle injections of cimetidine significantly reduced water intake in hypovolemic and hyperosmotic animals, but failed to alter water intake induced by central cholinergic stimulation by carbachol. We conclude that H 1 and H 2 brain histaminergic receptors are involved in inducing thirst during hyperosmolarity and hypovolemia and that H 1 histaminergic receptors located post-synaptically in relation to cholinergic pathways seem to be important in triggering drinking following central pharmacological cholinergic stimulation.

Effects of central and peripheral injections of apelin on fluid intake and cardiovascular parameters in rats

Previous studies have indicated that apelin, a novel peptide suggested to have some actions related to angiotensin peptides, has either a dipsogenic or an antidipsogenic effect and either increases or decreases blood pressure. The present study attempts to provide replication or understanding of these disparate effects. Neither central (lateral or third cerebral ventricle) nor peripheral (intravenous) administration of apelin induced water intake in sated rats, nor did it decrease water intake in deprived rats. It also had no effect on sodium appetite. Peripherally injected apelin had a hypotensive action in anesthetized rats, but had no consistent effect in awake, unrestrained rats. We conclude that apelin does not have reliable or robust effects on fluid intake or blood pressure in Sprague-Dawley rats under normal conditions, but discuss the possibility for a role of apelin in fluid homeostasis in selected physiological states.

Danggui–Buxue–Tang decoction has an anti-inflammatory effect in diabetic atherosclerosis rat model

Danggui–Buxue–Tang (DBT) is a famous traditional Chinese formula. We examined the anti-inflammatory effect of it in diabetic atherosclerosis rats. DBT (3 or 6 g/kg/day for 4 weeks) was orally administrated to the diabetic atherosclerosis rats, which were induced by nitric oxide inhibition ( l-NAME in drinking water, 1 mg/ml) plus high-fat diet. The concentrations of circulating inflammatory markers C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) and serum fructosamine were determined. The results showed that DBT had no direct effect in lowering serum fructosamine level, but can decrease the concentrations of CRP and TNF-α, produce a higher survival rate and less body weight loss, and decrease water intake in diabetic atherosclerosis in GK rats.

Oestrogen and weight loss decrease isoproterenol‐induced Fos immunoreactivity and angiotensin type 1 mRNA in the subfornical organ of female rats

Studies from our laboratory and others show that oestrogen reduces angiotensin II (Ang II)-induced water intake by ovariectomized rats. Elimination of endogenous oestrogen by ovariectomy causes weight gain that can be reversed or prevented by oestrogen replacement. Changes in body weight modify cardiovascular responses to Ang II but whether such changes have similar effects on central and behavioural responses to Ang II is unknown. The goal of this study was to evaluate the contributions of oestrogen and weight loss to isoproterenol (isoprenaline; Iso)-induced Fos immunoreactivity (IR) and to angiotensin type 1 (AT1) receptor mRNA in forebrain regions implicated in the control of fluid balance. Isoproterenol significantly increased Fos IR in the hypothalamic paraventricular and supraoptic nuclei, the subfornical organ (SFO), and the organum vasculosum of the lamina terminalis, but had no effect on AT1 mRNA expression. However, both Iso-induced Fos IR and the AT1 mRNA were attenuated in the SFO of the oestrogen and weight loss groups compared with that of the control group. Consequently, we examined the effect of weight loss on Iso-induced water intake and plasma renin activity (PRA) and found that weight loss decreased water intake after Iso, but had no effect on PRA. Thus, we propose that weight loss decreases Ang II-elicited water intake in the female rat by down-regulating the expression of the AT1 receptor.

High-fibre pelleted rations decrease water intake but do not improve physiological indexes of welfare in food-restricted female broiler breeders

1. A 3 × 2 factorial experiment was conducted with three diets and two lines of broiler breeder females to evaluate the contribution of low-energy rations for improving the welfare of feed-restricted birds during rearing. Experimental diets were fed from 6 to 16 weeks of age and were created by diluting a conventional grower (Control) ration containing 11·0 MJ ME/kg with 200 (8·8 MJ ME/kg) or 400 (6·6 MJ ME/kg) g oat hulls/kg using Optimoist to facilitate the pelleting process. Welfare was assessed by changes in behaviour and physiological variables at 8, 12 and 16 weeks of age. Birds were fed restricted quantities of feed to meet recommended body weight targets. 2. There was a decrease in the proportion of observations of drinking and an increase of preening in birds fed on the two experimental diets compared with the control. There was a linear decrease in litter moisture and the number of litter changes with increasing diet dilution, and water intake at 12 weeks was higher in the control than in the two experimental diets. There were no changes in physiological indexes of welfare (heterophil–lymphocyte ratio, plasma corticosterone and antibody responses) associated with the dietary treatments. 3. There were no important differences in the growth, behaviour or physiological responses to dietary treatment between the two lines of broiler breeders. Changes with age were similar to those reported in other experiments. 4. It was concluded that low-energy pelleted diets would improve litter conditions but not improve indexes of welfare in feed-restricted broiler breeders.

RANTES, MDC and SDF-1α, prevent the HIVgp120-induced food and water intake decrease in rats

Human immunodeficiency virus (HIV)-wasting syndrome might be facilitated by the HIVgp120 affecting the immunological system. We studied the effect (subchronic administration: 5 days) of HIVgp120, and a few immune-response mediators: regulated upon activation normal T-cell expressed and presumably secreted (RANTES), stromal derived factor-1α (SDF-1α), macrophage-derived chemokine (MDC), and their combination, on food and water intake in rats, motor control and pain perception. Eighty male adult Wistar rats received an intracerebroventricular (icv) administration of: vehicle 5 μl/day or 0.92 nmol daily of HIVgp120IIIB, RANTES, SDF-1α, or MDC, and the combination of RANTES + HIVgp120IIIB, SDF-1α + HIVgp120IIIB, or MDC + HIVgp120IIIB. Food and water intake was measured every day during administration, and 24 and 48 h after the last administration. Rats were also weighed the first and the last day of experiment in order to detect the impact of these treatments in the body weight. HIVgp120IIIB significantly decreased food and water intake. These rats gain less weight than the control (vehicle) and chemokines-treated subjects with exception of those treated with SDF-1α that also gain less weight. In addition, HIVgp120 deteriorated motor control. HIVgp120IIIB effects on food and water intake, and motor control were prevented by these chemokines. HIVgp120 + RANTES, HIVgp120 + SDF-1α, and SDF-1α alone induced hyperalgesia. Results suggest an interaction between HIVgp120 and the chemokine system to generate the HIV-wasting syndrome, the motor abnormalities and changes in pain perception.

Influence of a selective histamine H3 receptor antagonist on hypothalamic neural activity, food intake and body weight

This study was conducted to elucidate whether antagonistic targeting of the histamine H3 receptor increases hypothalamic histamine levels, in parallel with decreases in food intake and body weight. The competitive antagonist potency of a recently synthesized histamine H3 receptor antagonist, NNC 38-1049, was studied in intact HEK293 cells expressing human or rat histamine H3 receptor, in which NNC 38-1049 was allowed to antagonize the effect of the H3 receptor agonist R-alpha-methylhistamine on isoprenaline-induced accumulation of cAMP. The affinity of NNC 38-1049 for a number of variants of the histamine receptor was also determined. Following single dosing of normal rats with NNC 38-1049, hypothalamic histamine levels were assessed by means of microdialysis. Plasma and brain levels of NNC 38-1049 and acute effects on food intake and energy expenditure were followed after oral doses of 3-60 mg/kg. Potential side effects were examined with rat models of behaviour satiety sequence (BSS), pica behaviour and conditioned taste aversion (CTA). Intakes of food and water together with body weight were recorded for 15 days during daily dosing of dietary obese rats. NNC 38-1049 was found to be a highly specific and competitive antagonist towards both human and rat histamine H3 receptors, and measurable amounts of NNC 38-1049 were found in the plasma of rats following single oral doses of 3-60 mg/kg and in the brain after 15-60 mg/kg. Following single intraperitoneal injections of NNC 38-1049 (20 mg/kg), significant increases in extracellular histamine concentrations were observed. The same dose did not change BSS or pica behaviour acutely, nor did it induce CTA following repeated administration for 7 days. Reductions in food intake were seen very soon after administration, and occurred in a dose-dependent fashion. Energy expenditure was unchanged, but the respiratory quotient (RQ) tended to decrease at higher doses, indicating an increase in lipid oxidation. Twice daily administration of 20 mg/kg of NNC 38-1049 in old and dietary obese rats resulted in sustained reduction of food intake throughout a 2-week study, and was associated with a highly significant (P<0.01) decrease in body weight compared with controls (-18.4+/-3.4 vs +0.4+/-2.7 g). The same dose of NNC 38-1049 produced an acute decrease of water intake, but 24 h intakes were not significantly changed. The results of this study strongly support the idea that an increase in the hypothalamic concentration of histamine produces a specific reduction of food intake and that this effect can be translated into a decrease in body weight.

Gender Specificity of Programmed Plasma Hypertonicity and Hemoconcentration in Adult Offspring of Water-Restricted Rat Dams

We studied the impact of maternal water-restriction during rat pregnancy on newborn plasma composition, and determined the persistence of plasma composition alterations in adult offspring. Maternal dams were water-restricted from 10 days of pregnancy until term (21 days) and throughout lactation to increase plasma sodium levels by approximately 6 mEq/L. At 21 days of age, offspring were weaned, and subsequently maintained on ad libitum food and water until 12 weeks of age. Daily water and food intake was monitored. Blood samples and organs were collected from 1-day- and 12-week-old offspring. Hematocrit, plasma osmolality, sodium, and arginine vasopressin (AVP) levels were analyzed. Because water-restriction led to concomitant reduction in maternal food intake (ie, dehydration anorexia), henceforth these dams and their offspring are referred to as "water-deprived/food-reduced" rats. Water-deprived/food-reduced dams had significantly increased plasma sodium levels, reduced food intake, and lower body weight gain during pregnancy and lactation as compared to control dams. One-day-old newborns of water-deprived/food-reduced dams weighed 17% less and had increased plasma sodium levels, osmolality, and hematocrit. At 12 weeks of age, males exhibited 11% and females 19% reduction in body weight from controls. Notably, male offspring of water-deprived/food-reduced dams showed significantly elevated plasma sodium levels, osmolality, and hematocrit. Additionally, males demonstrated reduced adrenal growth and decreased water intake. Conversely, the female offspring had similar plasma osmolality with decreased sodium levels, though a persistently elevated hematocrit. No differences were evident in plasma AVP levels. Maternal water deprivation/food reduction is associated with increased newborn plasma osmolality and sodium levels and long-term physiologic changes in the offspring. The gender-specificity of programmed hyperosmolality, though not hemoconcentration, implicates differing pathways/mechanisms for these phenotypic alterations. The contributions of pregnancy hypertonicity versus nutrient restriction in the mechanism for programmed offspring phenotype remain to be elucidated.

Neuropeptide Y in the Paraventricular Nucleus of the Hypothalamus Increases Ethanol Intake in High‐ and Low‐Alcohol‐Drinking Rats

The behavioral effects of neuropeptide Y (NPY) attributed to its actions in the hypothalamus are complex and include effects on feeding, sedation, and the hypothalamic-pituitary-adrenal axis. NPY infused into the paraventricular nucleus (PVN) increases ethanol intake in unselected rats. High-alcohol-drinking (HAD1) and low-alcohol-drinking (LAD1) rats differ in basal NPY levels in the PVN, and HAD1, but not LAD1, rats exhibit decreases in ethanol intake after infusion of NPY into the ventricles. This study examined whether NPY infused into the PVN alters ethanol intake in HAD1 and LAD1 rats. Female HAD1 (n = 14) and LAD1 (n = 18) rats were given 24-hr free-choice continuous access to 15% (v/v) ethanol and water for 6 weeks and then implanted bilaterally with cannulas aimed at the PVN. Two weeks later, rats received a series of microinfusions, each separated by 1 week, that included four doses of NPY (0.0, 0.25, 0.5, and 1.0 microg). Ethanol, water, and food were available ad libitum after infusions. All rats received a final microinfusion of 1.0 microg of NPY, after which ethanol and water, but no food, were made available for 2 hr. During the 2 hr after infusion, NPY yielded dose-dependent increases in both water and food consumption. With food concurrently available, the 0.25- and 1.0-microg doses of NPY did not alter baseline ethanol intake, whereas the 0.5-microg dose increased ethanol intake. Infusion of 1.0 microg of NPY in the absence of food yielded a decrease in water intake and an increase in ethanol intake relative to the same dose in the presence of food. Twenty-four hours after infusion, there were no effects of NPY on water and food intake, and increases in ethanol intake were no longer apparent. Increases in ethanol intake after infusion of NPY into the PVN may depend on NPY dose and whether food is concurrently available.

Life style risks of Parkinson?s disease: Association between decreased water intake and constipation

Gastrointestinal dysfunction, especially constipation, is one of the major problems in the daily life of patients with Parkinson's disease (PD). About 60 to 80% of PD patients suffer from constipation. Several studies have proven that constipation appears about 10 to 20 years prior to motor symptoms. More recently, Abbott et al. have found from a large scale prospective study that lower frequency bowel movements predict the future risk of PD. Furthermore, Braak et al. have found that Lewy neuritis and Lewy bodies, the hallmarks of PD pathology, appear in the dorsal nucleus of vagus in the earliest stage of the disease and then extend upward through the brain stem to reach the substantia nigra in the third stage. They also hypothesize that some yet undefined toxins break through the mucosal barrier of the intestine and are incorporated into the axon terminal of the vagus nerve and transported in a retrograde manner to the vagus nucleus. In this study, we assessed bowel movements and nutritional status in Japanese patients with PD. We found that intake of water was significantly decreased in PD patients from early life and associated with their constipation. Ninety four patients with PD (M 50, F 44) were enrolled. Nutritional status was assessed using the Self-administered Diet History Questionnaire (DHQ). Total water intake was calculated from the consumption of coffee, green tea, and tea. We also questioned the behavior of water drinking from the early stage of life. The questionnaire for bowel movements concerned the frequency of defecation, age of onset of constipation, and age of onset of motor dysfunction. Less than one bowel movement in 3 days was defined as constipation. The nutritional status of PD patients did not differ significantly from those of controls though several studies have shown excess intake of animal fats or reduced consumption of coffee are risks in PD. In contrast, water intake was significantly lower in PD patients than controls (604.0+/-377.2 ml/d vs 909.5+/-531.6 ml/d; P<0.0001). Interestingly, PD patients tended not to feel thirsty and thus they had no desire to drink water throughout their life. Seventy four patients out of 94 (78.7 %) complained of constipation. Mean bowel frequency was once per 3.3+/-1.1 days and 71.1% of patients were defined as having constipation. Women suffered from constipation more frequently than men (82.4% vs 61.9 %). In 33 patients out of 74 (44.6 %), onset of constipation preceded motor disturbance by an average time of 18.1+/-18.8 years. Furthermore, the amount of water intake correlated inversely with the severity of constipation and the depletion of water intake preceded constipation in most cases. The present results support previous findings that constipation precedes the onset of motor dysfunction in PD. To our knowledge, this is the first report to point out latent water depletion in PD patients. It is not certain at present whether coffee or caffeine themselves are the protective factor for PD or alternatively the amount of water in coffee drinking is more essential. Prospective studies on a large scale are necessary to elucidate the real meaning of water depletion in PD.

Histaminergic H 1 and H 2 receptors located within the ventromedial hypothalamus regulate food and water intake in rats

The aim of the present study was to investigate the effect of the pharmacological blockade of histamine H 1 and H 2 receptors located within the ventromedial hypothalamus (VMH) on overnight food and water intake and on water intake elicited by two physiological stimuli: hyperosmolarity induced by an acute intragastric salt load and water deprivation. During the overnight period, the pharmacological blockade of both H 1 and H 2 VMH receptors significantly increased food intake and decreased water intake. In hyperosmotic rats, the blockade of H 1 VMH receptors reduced water intake, while the blockade of H 2 receptors in this same region yielded no significant effect. Additionally, in water-deprived rats, the blockade of both H 1 and H 2 receptors located within the VMH induced a significant decrease in water intake. The inhibitory effects on drinking behavior observed in this study do not seem to be a consequence of any “illness-inducing” effect provoked by the central administration of the antihistaminergic agents employed here, because an aversion test indicated that the injection of those compounds into the VMH does not induce any “illness-like” effect. In addition, the central administration of either mepyramine or cimetidine to dehydrated and hyperosmotic rats did not produce any reduction in locomotor activity measured in an open-field arena. Injections of the antihistaminergic agents used here into the regions that circumscribe the VMH produced no significant effects on water or food intake, indicating that the actions observed here may be specifically attributed to the set of histaminergic receptors situated within the VMH.

Dietary sodium regulates angiotensin AT1a and AT1b mRNA expression in mouse brain

Previous results showed that angiotensin (Ang) AT1a and AT1b receptor mRNA are expressed in mouse hypothalamus (HYP), brainstem (BS) and anterior pituitary (PIT). To extend these findings, we developed a real-time polymerase chain reaction (PCR) method to differentiate and quantify Ang AT1a and AT1b mRNA in mouse brain. An experiment was conducted in male C57Bl/6J mice to determine the effects of low and high dietary salt (0.04 or 8% NaCl for 2 weeks) on mRNA expression. Physiological measurements showed that high salt increased water intake (15.1 ± 0.6 ml/day), whereas low salt decreased water intake (3.2 ± 0.1 ml/day). There were no significant changes in body weight, hematocrit or plasma osmolality. Real-time PCR was effective in distinguishing AT1a and AT1b receptor mRNA. The PCR efficiencies for AT1a, AT1b and 18S ribosome were tested to be identical, making it possible to quantify mRNA levels. There were differences in angiotensin receptor expression, related to diet and brain region. In hypothalamus, both the high salt and low salt diet decreased AT1a expression (to 63 ± 4% and 62 ± 1%), although there were no changes in AT1b. In brainstem, there was a marked increase in AT1a (to 365 ± 60%) and AT1b (to 372 ± 23%) after high salt, although there was only a marked decrease for AT1b (to 23 ± 5%) after low salt. In anterior pituitary, both high salt and low salt diet increased AT1a expression (to 152 ± 8% and 123 ± 9%), although there were no changes in AT1b. Results document that both AT1 receptor subtypes are present in mouse hypothalamus, brainstem and anterior pituitary, and that there is differential regulation of expression in response to changes in dietary salt.

Effects of Fluoxetine Administration on Regional Galanin Expression in Obese Zucker Rat Hypothalamus

The aim of the present work was to study the potential involvement of hypothalamic galanin system in the anorectic mechanism of fluoxetine in obese Zucker rats. Male obese Zucker ( fa/fa ) rats were administered fluoxetine (10 mg/kg; i.p.) daily for two weeks. The control group was given 0.9% NaCl solution. Significant decreases in food intake, final body weight and total body fat were observed after fluoxetine treatment. Although fluoxetine-treated rats showed a decrease in urine elimination, this effect was not enough to compensate decreased water intake, leading to dehydration, as showed by decreased body water content. Chronic fluoxetine administration increased the numbers of galanin positively immunostained neural cells in medial and lateral preoptic areas, lateral hypothalamic area and paraventricular nucleus (rostral and magnocellular regions), without changes in dorsomedial, ventromedial, supraoptic, suprachiasmatic and arcuate nuclei. Taken into account that galanin stimulates appetite, these results could represent rather a compensatory response against reduced food intake than a direct anorectic mechanism. Changes in the magnocellular region of the hypothalamic paraventricular nucleus suggest a role for galanin neural circuits at this level in fluoxetine-induced hydro-osmotic impairment.