Effects of antifreeze protein from Lolium perenne L. (LpAFP) in the vitrification of in vitro-produced bovine embryos.

In the present study, the cryoprotective effects of Lolium perenne antifreeze protein (LpAFP) on the vitrification of bovine embryos were evaluated. In vitro-produced blastocysts were divided into two groups: the control group (CG) without the addition of LpAFP and the treatment group (TG) with the addition of 500 ng/ml of LpAFP in the equilibrium and vitrification solution. Vitrification was carried out by transferring the blastocysts to the equilibrium solution [7.5% ethylene glycol (EG) and 7.5% dimethyl sulfoxide (DMSO)] for 2 min and then to the vitrification solution (15% EG, 15% DMSO and 0.5M sucrose). The blastocysts were deposited on a cryotop device and submerged in liquid nitrogen. Warming was carried out in three steps in solutions with different sucrose concentrations (1.0, 0.5, and 0.0 M, respectively). Embryos were evaluated for re-expansion/hatching, the total cell count, and ultrastructural analysis. There was no significant difference in the re-expansion rate 24 h after warming; however, there was variation (P < 0.05) in the hatching rate in the TG and the total number of cells 24 h after warming was higher in the TG (114.87 ± 7.24) when compared with the CG (91.81 ± 4.94). The ultrastructural analysis showed changes in organelles related to the vitrification process but, in the TG, there was less damage to mitochondria and rough endoplasmic reticulum compared with the CG. In conclusion, the addition of 500 ng/ml of LpAFP during the vitrification of in vitro-produced bovine embryos improved the hatching rate and total cell number of blastocysts after warming and mitigated intracellular damage.

Intake, digestibility, ingestive behavior, and nitrogen balance of goats fed with diets containing residue from tamarind fruit.

This study is aimed at determining the maximum inclusion level of tamarind (Tamarindus indica) residues in the diet of goats on intake, digestibility, ingestive behavior, and nitrogen (N) balance. Twenty-four crossbred (Boer × undefined breed) castrated goat kids (5 months old and with an initial weight of 23.9 ± 0.3 kg) were assigned in a completely randomized design (4 treatments and 6 replicates). Diets consisted of Tifton 85 (Cynodon sp.) hay as the roughage (400 g/kg) source and concentrate (600 g/kg); the levels of tamarind residue inclusion were 0.0, 7.0, 14.0, and 21.0% on a dry matter (DM) basis. The experimental period lasted 23 days (15 of adaptation and 8 of sampling). Inclusion of tamarind residue in the goat kid diets did not affect (P > 0.05) the intake and digestibility of DM, crude protein, neutral detergent fiber (NDF), and total digestible nutrient; intake of N, urinary N, and retained N (g/day); time spent ruminating; numbers of times/day feeding, ruminating, or idling; eating efficiency of DM and NDF; number of boluses/day; and amount (g) of DM/bolus. However, there were a linear reduction in ether extract digestibility (P = 0.011) and a linear decreasing trend in non-fibrous carbohydrate digestibility (P = 0.083). The addition of tamarind residue had a positive linear effect (P = 0.041) on the time spent feeding and promoted a decreasing linear trend for the time spent idling (P = 0.063). It is recommended to include the residue from tamarind fruit at a level of 21% in diets for goat kids, as it does not affect nutrient intake and digestibility and the N balance.

Performance comparison between two equal stabilization ponds operating with and without sludge layer.

Stabilization ponds are a highly appropriate system for treating sewage in small to medium size communities. However, sludge accumulation at the pond bottom occurs with the passage of time, reducing the net pond volume, which, in principle, could affect its performance. The objective of this paper is to compare the behaviour of two equal ponds in parallel treating the same flow of municipal wastewater from an upflow anaerobic sludge blanket reactor in Brazil. Each pond treated a population equivalent of around 125 inhabitants. One pond had approximately 40% of its net volume occupied by sludge after 11 years of operation, while the other pond had previously undergone complete desludging. The study covers the removal of biochemical oxygen demand (BOD), chemical oxygen demand (COD), suspended solids (SS), nitrogen fractions and coliforms. Owing to the presence of a sludge layer, the theoretical hydraulic retention time (HRT) was lower in the pond without sludge. For BOD, COD, SS and Escherichia coli there were no significant differences (Wilcoxon matched-pairs test) between both ponds. The pond without sludge had significantly better removal efficiencies in terms of total Kjeldahl nitrogen and ammonia-N. The sludge layer probably allowed the occurrence of removal mechanisms that compensated for the reduction caused in the HRT.

Angiotensin II induces Fat1 expression/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation.

Fat1 is an atypical cadherin that controls vascular smooth muscle cell (VSMC) proliferation and migration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) is an important source of reactive oxygen species (ROS) in VSMCs. Angiotensin II (Ang II) induces the expression and/or activation of both Fat1 and Nox1 proteins. This study tested the hypothesis that Ang II-induced Fat1 activation and VSMC migration are mediated by Nox1-dependent ROS generation and redox signaling. Studies were performed in cultured VSMCs from Sprague­Dawley rats. Cells were treated with Ang II (1 µmol/L) for short (5 to 30 min) or long term stimulations (3 to 12 h) in the absence or presence of the antioxidant apocynin (10 µmol/L), extracellular-signal-regulated kinases 1/2 (Erk1/2) inhibitor PD98059 (1 µmol/L), or Ang II type 1 receptor (AT1R) valsartan (1 µmol/L). siRNA was used to knockdown Nox1 or Fat1. Cell migration was determined by Boyden chamber assay. Ang II increased Fat1 mRNA and protein levels and promoted Fat1 translocation to the cell membrane, responses that were inhibited by AT1R antagonist and antioxidant treatment. Downregulation of Nox1 inhibited the effects of Ang II on Fat1 protein expression. Nox1 protein induction, ROS generation, and p44/p42 MAPK phosphorylation in response to Ang II were prevented by valsartan and apocynin, and Nox1 siRNA inhibited Ang II-induced ROS generation. Knockdown of Fat1 did not affect Ang II-mediated increases in Nox1 expression or ROS. Inhibition of p44/p42 MAPK phosphorylation by PD98059 abrogated the Ang II-induced increase in Fat1 expression and membrane translocation. Knockdown of Fat1 inhibited Ang II-induced VSMC migration, which was also prevented by valsartan, apocynin, PD98059, and Nox1 siRNA. Our findings indicate that Ang II regulates Fat1 expression and activity and induces Fat1-dependent VSMC migration via activation of AT1R, ERK1/2, and Nox1-derived ROS, suggesting a role for Fat1 downstream of Ang II signaling that leads to vascular remodeling.

Aberrant Brain Signal Variability and COMT Genotype in Chronic TMD Patients.

The analysis of brain signal variability is a promising approach to understand pathological brain function related to chronic pain. This study investigates whether blood-oxygen-level-dependent signal variability (BOLDSV) in specific frequency bands is altered in temporomandibular disorder (TMD) and correlated to its clinical features. Twelve patients with chronic myofascial TMD and 24 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. The BOLDSV was measured as the standard deviation of the BOLD time series at each voxel and compared between groups. We also examined the potential relationship between the BOLDSV and the catechol-O-methyltransferase (COMT) Val158Met polymorphism. We assessed sensory-discriminative pain in the craniofacial region, pain sensitivity to sustained masseteric pain challenge, and TMD pain frequency for clinical correlation. Patients displayed reduced BOLDSV in the dorsolateral prefrontal cortex (dlPFC) as compared with HC in all frequency bands. In the slow-3 band, patients also showed reduced BOLDSV in the medial dorsal thalamus, primary motor cortex (M1), and primary somatosensory cortex (S1) and heightened BOLDSV in the temporal pole. Notably, we found a significant correlation between lower BOLDSV (slow-3) in the orofacial M1/S1 regions and higher clinical pain (intensity/area) and higher sensitivity of the masseter muscle pain. Moreover, lower BOLDSV (slow-3) in the dlPFC and ventrolateral PFC was associated with a higher TMD pain frequency. Participants who had the COMT158Met substitution exhibited lower BOLDSV in the dlPFC and higher BOLDSV in the temporal pole as compared with participants without the COMT158Met substitution. An increasing number of Met alleles was associated with lower dlPFC and greater temporal pole BOLDSV in both HC and TMD groups. Together, we demonstrated that chronic TMD patients exhibit aberrant BOLDSV in the top-down pain modulatory and sensorimotor circuits associated with their pain frequency and severity. COMT Val158Met polymorphism might affect clinical symptoms in association with regional brain signal variability, specifically involved in cognitive and emotional regulation of pain.

Effects of condensed tannin-amended cassava silage blend diets on feeding behavior, digestibility, nitrogen balance, milk yield and milk composition in dairy goats.

Condensed tannins (CTs) are phenolic compounds derived from secondary plant metabolism that act as part of the plant's chemical defense system against pathogen invasion and herbivorous attack. This study aimed to evaluate the intake, digestibility, nitrogen (N) balance, production and composition of milk from goats fed cassava silage with added levels of CTs. Eight Anglo-Nubian goats with a mean BW of 40 ±â€¯2.0 kg were distributed in a double Latin square design with four levels of CTs (0, 25, 50 and 75 g/kg DM) with four 20-day periods with 15 days of adaptation and five evaluation days for each period. No differences were observed in DM, NDF, CP intake and feed conversion (grams of DM intake (DMI) per gram of milk produced); however, when expressed as percent of BW, DMI showed a quadratic increase to 29.1 g/kg. As the level of supplemented CTs increased in the diet, the CP digestibility (P = 0.023), NDF (P = 0.044), non-fiber carbohydrates (NFC; P = 0.032) and total digestible nutrients (P = 0.033) exhibited a linear decrease. Furthermore, the addition of CTs to cassava silage induced a linear increase in N-fecal excretion (P = 0.014) and a positive quadratic effect on N-retained (P = 0.014) and N-balance (P = 0.024) as well as a positive quadratic trend in N-digested (P = 0.092). Milk urea N (P = 0.023) decreased linearly. The addition of CTs to cassava silage had a positive quadratic effect on ruminating time (P = 0.011). In addition, comparing the use or non-use from the orthogonal contrast test, the inclusion of CTs in goat diet increased water and N-intake, CP and NDF digestibility, spent time eating and ruminating and N-balance and decreased milk production corrected3.5%, fat milk content, milk urea N and dry defatted extract of milk. Thus, adding CTs to cassava silage at 25 g/kg total DM promoted goats' greater use of the diet without impairing feed conversion and the quality of goat milk produced. Dietary levels of 50 and 75 g/kg total DM are not recommended because under the conditions of this study, they reduced the productive efficiency of dairy goats.

The essential oil of Hyptis crenata Pohl ex Benth. presents an antiedematogenic effect in mice.

Hyptis crenata, commonly known as "salva-do-Marajó", "hortelã-do-campo", and "hortelãzinha", is used in folk medicine in Northeast Brazil as tea or infusion to treat inflammatory diseases. Due to the pharmacological efficacy and the low toxicity of the essential oil of Hyptis crenata (EOHc), we decided to investigate the EOHc antiedematogenic effect in experimental models of inflammation. EOHc was administrated orally at doses of 10-300 mg/kg to male Swiss albino mice. Paw edema was induced by subcutaneous injection in the right hind paw of inflammatory stimuli (carrageenan, dextran, histamine, serotonin, and bradykinin) 60 min after administration of EOHc. EOHc significantly inhibited the induced edema. The inhibitory effect of EOHc on dextran-induced edema extended throughout the experimental time. For the 30, 100, and 300 mg/kg doses of EOHc, the inhibition was of 40.28±1.70, 51.18±2.69, and 59.24±2.13%, respectively. The EOHc inhibitory effect on carrageenan-induced edema started at 10 mg/kg at the second hour (h) and was maintained throughout the observation period. At 30, 100, and 300 mg/kg doses the inhibition started earlier, from 30 min. At the edema peak of 180 min, 56, 76, and 82% inhibition was observed for 30, 100, and 300 mg/kg doses, respectively. Additionally, the effect of EOHc on carrageenan-induced paw edema was influenced by the time of administration. The EOHc also inhibited myeloperoxidase activity. In conclusion, the EOHc showed a potent effect, both preventing and reversing the edema, consistent with its anti-inflammatory use in folk medicine.

Evaluation of Hypoglycemic Therapy Through Physical Exercise in n5STZ-Induced Diabetes Rats.

BACKGROUND: Diabetes mellitus is a syndrome with multiple etiologies involving insulin, in which there is a lack of production and/or loss of sensitivity to this hormone resulting in insulin resistance. Treatment and control of this disease requires changes in diet, use of medication, and lifestyle, such as physical activity. These modifications may compromise quality-of-life if there is no proper guidance for the treatment or alert to possible complications caused by the disease. METHODS: This study aimed to evaluate biochemical and hematological parameters, and to assess brain derived neurotrophic factor levels in diabetic Wistar rats submitted to chronic physical exercise. RESULTS: The results demonstrated an increase in plasma concentration of brain-derived neurotrophic factor (BDNF) in association with hyperglycemia reduction in diabetic animals. DISCUSSION: The results obtained suggest that there is a regulation of glucose homeostasis between peripheral tissues and the central nervous system. Exercise-induced BDNF also improved levels of glycemia, body weight, and dyslipidemia. In hematological evaluation, BDNF increase was positively correlated with an improvement in leukocyte parameters. Electrophoresis analyses demonstrated a reduction in levels of pro-inflammatory proteins, lipoprotein fractions, and albumin preservation in diabetic animals trained with elevated concentration of plasma BDNF. CONCLUSION: In conclusion, this study demonstrated that chronic exercise was able to elevate BDNF levels in plasma, which resulted directly in positive hypoglycemic activity in diabetic animals and a reduction of the metabolic syndrome associated with diabetes mellitus.

Radicicol enhances the regeneration of skeletal muscle injured by crotoxin via decrease of NF-kB activation.

This study evaluated cellular and molecular effects of radicicol, a heat shock protein (HSP) inducer, on the regeneration of skeletal muscle injured by crotoxin, the main toxin isolated from Crotalus durissus terrificus venom. Regenerating muscles treated with radicicol had decreased NF-kB activation. Differentiating myoblasts treated with radicicol showed reduced number of NF-kB positive nuclei and increased fusion index. The results suggest that radicicol enhances regeneration of muscle by attenuating NF-kB activation and increasing myogenic differentiation.

µ-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism.

Clinicians have the dilemma of prescribing opioid or nonopioid analgesics to chronic pain patients; however, the impact of pain on our endogenous µ-opioid system and how our genetic profile (specifically catechol-O-methyltransferase [COMT] polymorphisms) impacts its activation are currently unknown. Twelve chronic temporomandibular disorder (TMD) patients and 12 healthy controls (HCs) were scanned using positron emission tomography (PET) with [11C]carfentanil, a selective radioligand for µ-opioid receptors (µORs). The first 45 min of each PET measured the µOR nondisplaceable binding potential (BPND) at resting state, and the last 45 min consisted of a 20-min masseteric pain challenge with an injection of 5% hypertonic saline. Participants were also genotyped for different COMT alleles. There were no group differences in µOR BPND at resting state (early phase). However, during the masseteric pain challenge (late phase), TMD patients exhibited significant reductions in µOR BPND (decreased [11C]carfentanil binding) in the contralateral parahippocampus (P = 0.002) compared to HCs. The µOR BPND was also significantly lower in TMD patients with longer pain chronicity (P < 0.001). When considering COMT genotype and chronic pain suffering, TMD patients with the COMT158Met substitution had higher pain sensitivity and longer pain chronicity with a 5-y threshold for µOR BPND changes to occur in the parahippocampus. Together, the TMD diagnosis, COMT158Met substitution, and pain chronicity explained 52% of µOR BPND variance in the parahippocampus (cumulative R2 = 52%, P < 0.003, and HC vs. TMD Cohen's effect size d = 1.33 SD). There is strong evidence of dysregulation of our main analgesic and limbic systems in chronic TMD pain. The data also support precision medicine by helping identify TMD patients who may be more susceptible to chronic pain sensitivity and opioid dysfunction based on their genetic profile.

Brain Functional Changes before, during, and after Clinical Pain.

This study used an emerging brain imaging technique, functional near-infrared spectroscopy (fNIRS), to investigate functional brain activation and connectivity that modulates sometimes traumatic pain experience in a clinical setting. Hemodynamic responses were recorded at bilateral somatosensory (S1) and prefrontal cortices (PFCs) from 12 patients with dentin hypersensitivity in a dental chair before, during, and after clinical pain. Clinical dental pain was triggered with 20 consecutive descending cold stimulations (32° to 0°C) to the affected teeth. We used a partial least squares path modeling framework to link patients' clinical pain experience with recorded hemodynamic responses at sequential stages and baseline resting-state functional connectivity (RSFC). Hemodynamic responses at PFC/S1 were sequentially elicited by expectation, cold detection, and pain perception at a high-level coefficient (coefficients: 0.92, 0.98, and 0.99, P < 0.05). We found that the pain ratings were positively affected only at a moderate level of coefficients by such sequence of functional activation (coefficient: 0.52, P < 0.05) and the baseline PFC-S1 RSFC (coefficient: 0.59, P < 0.05). Furthermore, when the dental pain had finally subsided, the PFC increased its functional connection with the affected S1 orofacial region contralateral to the pain stimulus and, in contrast, decreased with the ipsilateral homuncular S1 regions ( P < 0.05). Our study indicated for the first time that patients' clinical pain experience in the dental chair can be predicted concomitantly by their baseline functional connectivity between S1 and PFC, as well as their sequence of ongoing hemodynamic responses. In addition, this linked cascade of events had immediate after-effects on the patients' brain connectivity, even when clinical pain had already ceased. Our findings offer a better understating of the ongoing impact of affective and sensory experience in the brain before, during, and after clinical dental pain.

Diversity of Anopheles mosquitoes from four landscapes in the highest endemic region of malaria transmission in Brazil.

Malaria transmission in South America is overwhelmingly located in the Amazon region with limited cases outside that biome. A key factor in the mitigation of malaria transmission is the determination of vector diversity and bionomics in endemic areas. Anopheles mosquitoes were collected in four different landscapes of Cruzeiro do Sul-Acre, the current area with highest malaria transmission in Brazil. We performed adult mosquito collections every three months over two years and associated vector occurrence with local abiotic factors. A total of 1,754 Anopheles belonging to nine species were collected, but only four of them (An. albitarsis s.l. Lynch-Arribalzaga, An. braziliensis Chagas, An. peryassui Dyar and Knab, and An. triannulatus Neiva and Pinto) represented 77.1% of the total. Vector density and diversity was uneven across field sites and collection periods. Higher Anopheles abundance (54.8%) and richness were observed in a deforested palm tree area (IFC), with An. braziliensis the most frequent mosquito (40.5%). Only 7.3% of mosquitoes were collected in the SAB village, but 66.4% of them were An. darlingi and An. oswaldoi, species often regarded as primary and secondary vectors of malaria in the Amazon region. A distinct biting preference was observed between 18:00-19:40. The distance from the nearest breeding site and minimum temperature explained 41.6% of the Anopheles community composition. Our data show that the Anopheles species composition may present great variation on a microgeographic scale.

Molecular confirmation of the specific status of Anopheles halophylus (Diptera: Culicidae) and evidence of a new cryptic species within An. triannulatus in central Brazil.

Anopheles halophylus Silva-do-Nascimento & Lourenço-de-Oliveira was recently described using morphological and biological variants in specimens previously identified as Anopheles triannulatus (Neiva & Pinto). Because these two species occur in sympatry in central Brazil, we used allozymes to determine the extent of gene flow to confirm that they are different species. Of 11 allozyme loci analyzed, one (Mpi) was found to be diagnostic for An. halophylus and An. triannulatus, confirming their specific status. This locus revealed a second sibling species within An. triannulatus sensu lato. An. halophylus and the new undescribed species were confirmed using random amplified polymorphic DNA markers that showed moderate genetic divergence among these three sympatric and closely related taxa (D = 0.145-0.428). Moreover, this marker indicates that An. halophylus and the new species are more closely related to each other than either is to An. triannulatus.

The essential oil of Hyptis crenata Pohl ex Benth. presents an antiedematogenic effect in mice

Hyptis crenata, commonly known as "salva-do-Marajó", "hortelã-do-campo", and "hortelãzinha", is used in folk medicine in Northeast Brazil as tea or infusion to treat inflammatory diseases. Due to the pharmacological efficacy and the low toxicity of the essential oil of Hyptis crenata (EOHc), we decided to investigate the EOHc antiedematogenic effect in experimental models of inflammation. EOHc was administrated orally at doses of 10-300 mg/kg to male Swiss albino mice. Paw edema was induced by subcutaneous injection in the right hind paw of inflammatory stimuli (carrageenan, dextran, histamine, serotonin, and bradykinin) 60 min after administration of EOHc. EOHc significantly inhibited the induced edema. The inhibitory effect of EOHc on dextran-induced edema extended throughout the experimental time. For the 30, 100, and 300 mg/kg doses of EOHc, the inhibition was of 40.28±1.70, 51.18±2.69, and 59.24±2.13%, respectively. The EOHc inhibitory effect on carrageenan-induced edema started at 10 mg/kg at the second hour (h) and was maintained throughout the observation period. At 30, 100, and 300 mg/kg doses the inhibition started earlier, from 30 min. At the edema peak of 180 min, 56, 76, and 82% inhibition was observed for 30, 100, and 300 mg/kg doses, respectively. Additionally, the effect of EOHc on carrageenan-induced paw edema was influenced by the time of administration. The EOHc also inhibited myeloperoxidase activity. In conclusion, the EOHc showed a potent effect, both preventing and reversing the edema, consistent with its anti-inflammatory use in folk medicine.

Different Brain Responses to Pain and Its Expectation in the Dental Chair.

A dental appointment commonly prompts fear of a painful experience, yet we have never fully understood how our brains react to the expectation of imminent tooth pain once in a dental chair. In our study, 21 patients with hypersensitive teeth were tested using nonpainful and painful stimuli in a clinical setting. Subjects were tested in a dental chair using functional near-infrared spectroscopy to measure cortical activity during a stepwise cold stimulation of a hypersensitive tooth, as well as nonpainful control stimulation on the same tooth. Patients' sensory-discriminative and emotional-cognitive cortical regions were studied through the transition of a neutral to a painful stimulation. In the putative somatosensory cortex contralateral to the stimulus, 2 well-defined hemodynamic peaks were detected in the homuncular orofacial region: the first peak during the nonpainful phase and a second peak after the pain threshold was reached. Moreover, in the upper-left and lower-right prefrontal cortices, there was a significant active hemodynamic response in only the first phase, before the pain. Subsequently, the same prefrontal cortical areas deactivated after a painful experience had been reached. Our study indicates for the first time that pain perception and expectation elicit different hemodynamic cortical responses in a dental clinical setting.

Natriuretic and kaliuretic effects of central acute cadmium administration in rats.

We studied the acute effects of cadmium third ventricle injections on renal excretion of water, sodium and potassium in rats previously submitted to an oral water load equivalent to 10% of their body weight. Injections of cadmium chloride (0.03, 0.3, and 3.0 nmol/rat) significantly increased sodium and potassium renal excretion without changing urine flow. Pretreatment with losartan, an angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central cadmium administration) inhibits the natriuretic effect of this metal, being unable to reverse its kaliuretic effect. Pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central cadmium administration) abolishes both the natriuretic and the kaliuretic response of cadmium. The data clearly show that cadmium injections into the third ventricle disturb central regulation of renal function leading to an increased renal loss of sodium and potassium. It is also evident that the natriuretic action of the metal depends on an increase in brain angiotensin II release. Also, the functional integrity of calcium channels is required for the expression of both the natriuretic and the kaliuretic effects of the metal.

Central administration of zinc increases renal sodium and potassium excretion in rats.

The aim of the present study was to investigate the effect of acute third ventricle injections of zinc on the brain control of renal sodium and potassium excretion. Adult Wistar male rats received third ventricle injections of zinc acetate in three different doses (0.03, 0.3 and 3.0 nmol/rat). Third ventricle administration of zinc acetate provoked a significant intensification of natriuresis and kaliuresis as compared to sodium acetate-treated controls. When rats were pretreated with losartan, a selective angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central zinc injection) the increase in both natriuresis and kaliuresis was abolished. Furthermore, pretreatment with gadolinium, a calcium channel blocker (0.3 nmol/rat into the third ventricle 20 min before central zinc injection), also blunted the increase in renal sodium and potassium excretion seen in animals receiving zinc alone. In a group of rats receiving the same water load used in the previous experiments, the injection of zinc acetate into the third ventricle (3.0 nmol/rat) did not modify arterial blood pressure. It is suggested that zinc in the central nervous system may be involved in the control of renal sodium and potassium excretion by a mechanism unrelated to blood pressure increase. It is also shown that both natriuretic and kaliuretic actions of zinc depend on AT1 receptor activation. Whatever should be the mechanism(s) related to the central effects of zinc here evidenced, the functional integrity of calcium channels is required.

Central lead administration induces natriuretic and kaliuretic effects in rats.

The aim of the present experiments was to discern whether central acute lead injections affect brain control of renal function. Adult Wistar male rats received third-ventricle injections of lead acetate in three different doses (0.03, 0.3, and 3.0 nmol/rat). Lead acetate induced a significant increase in renal excretion of sodium and potassium. Pretreatment with losartan, a selective angiotensin II AT1 receptor antagonist (10.8 nmol/rat into the third ventricle 10 min before central lead injection), inhibits lead-induced natriuretic and kaliuretic effects. In addition, pretreatment with gadolinium, a calcium-channel blocker (0.3 nmol/rat into the third ventricle 20 min before central lead administration), reversed the increase in renal excretion of sodium and potassium provoked by central lead administration. Taken together, the data presented here suggest that lead injected into the third ventricle increases renal excretion of sodium and potassium by a mechanism that depends on the functional integrity of central angiotensin II AT1 receptors and calcium channels.

Effect of third ventricle administration of L-694,247, a selective 5-HT1D receptor agonist, on water intake in rats.

L-694,247, a selective 5-HT1D receptor agonist, injected directly into the third ventricle (2.5, 5.0, and 10.0 micrograms/rat) of dehydrated rats induced a dose-dependent partial blockade of water intake. Injected in this way, the compound abolishes drinking behavior induced by third ventricle administration of carbachol (2 micrograms/rat), angiotensin II (5 ng/rat), and isoproterenol (40 micrograms/rat). In addition, intraventricular injections of L-694,247 did not modify water intake in normohydrated rats. The effects of L-694,247 are due to a specific interaction with 5-HT1D receptors, because its inhibitory effect on water intake in dehydrated rats is blocked by the previous administration of a 5-HT1D antagonist, GR 127935 (5 micrograms/rat), directly into the third ventricle. It is concluded that central 5-HT1D receptor activation disrupts the functional integrity of central pathways related to drinking behavior.