AT1a receptor signaling is required for basal and water deprivation-induced urine concentration in AT1a receptor-deficient mice

It is well recognized that ANG II interacts with arginine vasopressin (AVP) to regulate water reabsorption and urine concentration in the kidney. The present study used ANG II type 1a (AT(1a)) receptor-deficient (Agtr1a(-/-)) mice to test the hypothesis that AT(1a) receptor signaling is required for basal and water deprivation-induced urine concentration in the renal medulla. Eight groups of wild-type (WT) and Agtr1a(-/-) mice were treated with or without 24-h water deprivation and 1-desamino-8-d-AVP (DDAVP; 100 ng/h ip) for 2 wk or with losartan (10 mg/kg ip) during water deprivation. Under basal conditions, Agtr1a(-/-) mice had lower systolic blood pressure (P < 0.01), greater than threefold higher 24-h urine excretion (WT mice: 1.3 ± 0.1 ml vs. Agtr1a(-/-) mice: 5.9 ± 0.7 ml, P < 0.01), and markedly decreased urine osmolality (WT mice: 1,834 ± 86 mosM/kg vs. Agtr1a(-/-) mice: 843 ± 170 mosM/kg, P < 0.01), without significant changes in 24-h urinary Na(+) excretion. These responses in Agtr1a(-/-) mice were associated with lower basal plasma AVP (WT mice: 105 ± 8 pg/ml vs. Agtr1a(-/-) mice: 67 ± 6 pg/ml, P < 0.01) and decreases in total lysate and membrane aquaporin-2 (AQP2; 48.6 ± 7% of WT mice, P < 0.001) and adenylyl cyclase isoform III (55.6 ± 8% of WT mice, P < 0.01) proteins. Although 24-h water deprivation increased plasma AVP to the same levels in both strains, 24-h urine excretion was still higher, whereas urine osmolality remained lower, in Agtr1a(-/-) mice (P < 0.01). Water deprivation increased total lysate AQP2 proteins in the inner medulla but had no effect on adenylyl cyclase III, phosphorylated MAPK ERK1/2, and membrane AQP2 proteins in Agtr1a(-/-) mice. Furthermore, infusion of DDAVP for 2 wk was unable to correct the urine-concentrating defects in Agtr1a(-/-) mice. These results demonstrate that AT(1a) receptor-mediated ANG II signaling is required to maintain tonic AVP release and regulate V(2) receptor-mediated responses to water deprivation in the inner medulla.     

Exogenous sodium sulfide improves morphological and physiological responses of a hybrid Populus species to nitrogen dioxide

Gaseous nitrogen dioxide (NO₂) can disturb normal plant growth and trigger complex physiological responses. NO₂-induced responses are influenced by biotic or abiotic factors. In this study, we investigated the effects of exogenous sodium sulfide (Na₂S, 5 mmol L⁻¹) on epidermis and stomata related physico-chemical responses of hybrid poplar cuttings (Pouplus alba × P. berolinensis) to gaseous NO₂ (4 μl 1⁻¹) for three time periods (0, 14 and 48 h). We also investigated hydrogen sulfide (H₂S), nitrate-nitrogen and nitrate reductase activity (NR) in control and Na₂S treated plants. Our results showed that NO₂ exposure for 48 h led to the decline of NR, maximal PSII quantum yield (F_v/F_m), net photosynthetic rate (P_n), and dark respiration rate (R_d). The maximum rate for the post-illumination carbon dioxide burst (PIB) occurred in 48-h exposed leaves 13–15 s after darkening. Moreover, NO₂ exposure resulted in a significant increase in nitrogen percentage (from 0 to 33%) and a decrease in the macro and micro-elements of leaf surface. Spraying Na₂S aqueous solution on the leaf surfaces significantly increased the thicknesses of palisade/spongy tissue and H₂S content. Na₂S pretreatment alleviated NO₂-caused toxic effects as indicated by increased NR and higher values of P_n, F_v/F_m, and actual photochemical efficiency in light (ФPSII) compared with the control. Na₂S pretreatment had no significant impacts on PIB-based photorespiration or elements composition of a leaf surface.     

Intranasal oxytocin,but not vasopressin,augments neural responses to toddlers in human fathers

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT before one scan and placebo before the other scan (n = 15) or 20 IU intranasal AVP before one scan and placebo before the other scan (n = 15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression.     

Measurement of plasma hydrogen sulfide in vivo and in vitro

The gasotransmitter hydrogen sulfide is known to regulate multiple cellular functions during normal and pathophysiological states. However, a paucity of concise information exists regarding quantitative amounts of hydrogen sulfide involved in physiological and pathological responses. This is primarily due to disagreement among various methods employed to measure free hydrogen sulfide. In this article, we describe a very sensitive method of measuring the presence of H₂S in plasma down to nanomolar levels, using monobromobimane (MBB). The current standard assay using methylene blue provides erroneous results that do not actually measure H₂S. The method presented herein involves derivatization of sulfide with excess MBB in 100 mM Tris–HCl buffer (pH 9.5, 0.1 mM DTPA) for 30 min in 1% oxygen at room temperature. The fluorescent product sulfide-dibimane (SDB) is analyzed by RP-HPLC using an eclipse XDB-C18 (4.6 × 250 mm) column with gradient elution by 0.1% (v/v) trifluoroacetic acid in acetonitrile. The limit of detection for sulfide-dibimane is 2 nM and the SDB product is very stable over time, allowing batch storage and analysis. In summary, our MBB method is suitable for sensitive quantitative measurement of free hydrogen sulfide in multiple biological samples such as plasma, tissue and cell culture lysates, or media.     

Analytical measurement of discrete hydrogen sulfide pools in biological specimens

Hydrogen sulfide (H₂S) is a ubiquitous gaseous signaling molecule that plays a vital role in numerous cellular functions and has become the focus of many research endeavors, including pharmacotherapeutic manipulation. Among the challenges facing the field is the accurate measurement of biologically active H₂S. We have recently reported that the typically used methylene blue method and its associated results are invalid and do not measure bona fide H₂S. The complexity of analytical H₂S measurement reflects the fact that hydrogen sulfide is a volatile gas and exists in the body in various forms, including a free form, an acid-labile pool, and bound as sulfane sulfur. Here we describe a new protocol to discretely measure specific H₂S pools using the monobromobimane method coupled with RP-HPLC. This new protocol involves selective liberation, trapping, and derivatization of H₂S. Acid-labile H₂S is released by incubating the sample in an acidic solution (pH 2.6) of 100 mM phosphate buffer with 0.1 mM diethylenetriaminepentaacetic acid (DTPA), in an enclosed system to contain volatilized H₂S. Volatilized H₂S is then trapped in 100 mM Tris–HCl (pH 9.5, 0.1 mM DTPA) and then reacted with excess monobromobimane. In a separate aliquot, the contribution of the bound sulfane sulfur pool was measured by incubating the sample with 1 mM TCEP (tris(2-carboxyethyl)phosphine hydrochloride), a reducing agent, to reduce disulfide bonds, in 100 mM phosphate buffer (pH 2.6, 0.1 mM DTPA), and H₂S measurement was performed in a manner analogous to the one described above. The acid-labile pool was determined by subtracting the free hydrogen sulfide value from the value obtained by the acid-liberation protocol. The bound sulfane sulfur pool was determined by subtracting the H₂S measurement from the acid-liberation protocol alone compared to that of TCEP plus acidic conditions. In summary, our new method allows very sensitive and accurate measurement of the three primary biological pools of H₂S, including free, acid-labile, and bound sulfane sulfur, in various biological specimens.     

Physiology of spontaneous [Ca2+]i oscillations in the isolated vasopressin and oxytocin neurones of the rat supraoptic nucleus

The magnocellular vasopressin (AVP) and oxytocin (OT) neurones exhibit specific electrophysiological behaviour, synthesise AVP and OT peptides and secrete them into the neurohypophysial system in response to various physiological stimulations. The activity of these neurones is regulated by the very same peptides released either somato-dendritically or when applied to supraoptic nucleus (SON) preparations in vitro. The AVP and OT, secreted somato-dendritically (i.e. in the SON proper) act through specific autoreceptors, induce distinct Ca²⁺ signals and regulate cellular events. Here, we demonstrate that about 70% of freshly isolated individual SON neurones from the adult non-transgenic or transgenic rats bearing AVP (AVP-eGFP) or OT (OT-mRFP1) markers, produce distinct spontaneous [Ca²⁺]_i oscillations. In the neurones identified (through specific fluorescence), about 80% of AVP neurones and about 60% of OT neurones exhibited these oscillations. Exposure to AVP triggered [Ca²⁺]_i oscillations in silent AVP neurones, or modified the oscillatory pattern in spontaneously active cells. Hyper- and hypo-osmotic stimuli (325 or 275 mOsmol/l) respectively intensified or inhibited spontaneous [Ca²⁺]_i dynamics. In rats dehydrated for 3 or 5 days almost 90% of neurones displayed spontaneous [Ca²⁺]_i oscillations. More than 80% of OT-mRFP1 neurones from 3 to 6-day-lactating rats were oscillatory vs. about 44% (OT-mRFP1 neurones) in virgins. Together, these results unveil for the first time that both AVP and OT neurones maintain, via Ca²⁺ signals, their remarkable intrinsic in vivo physiological properties in an isolated condition.     

Salivary vasopressin increases following intranasal oxytocin administration

Extant research has documented the effects of intranasal administration of oxytocin (OT), and to a lesser degree Arginine Vasopressin (AVP) – two structurally-related neuropeptides – on brain and behaviour, yet the effects of exogenous manipulation of one on circulating levels of the other remain unknown. Studies have shown that OT administration impacts the peripheral levels of numerous hormones; however, whether OT administration also increases AVP concentrations has not been explored. Utilizing a double-blind placebo-controlled within-subject design, ten male and female subjects provided ten saliva samples over four consecutive hours: at baseline and nine times following OT administration. Results indicate that salivary AVP increased in the first hour following OT manipulation (OT condition: mean AVP = 2.17 pg/ml, SE = 28, placebo condition: mean AVP = 1.42 pg/ml, SE = .18) but returned to baseline levels at the next assessment (80 min) and remained low for the remaining period. Similar to OT, AVP showed high degree of individual stability and baseline levels of AVP correlated with AVP concentrations at the first and second post-administration hours regardless of drug condition (Pearson r = .85–.93). Validity of salivary AVP ELISA measurement was verified by demonstrating individual stability of salivary AVP over a six-month period (r = .70, p < .000) as well correlation with plasma levels over the same period (r = .32, p = .037) in a sample of 45 young adults who did not participate in the current study. Overall, findings suggest a potential crosstalk between OT and AVP and indicate that baseline levels of the two neuropeptides may shape the degree to which these systems respond to exogenous manipulation.     

Discovery of medium ring thiophosphorus based heterocycles as antiproliferative agents

Hydrogen sulfide (H₂S) has been investigated for its potential in therapy. Recently, we reported novel H₂S donor molecules based on a thiophosphorus core, which slowly release H₂S and have improved anti-proliferative activity in cancer cell lines compared to the most widely studied H₂S donor GYY4137 (1). Herein, we have prepared new thiophosphorus organic H₂S donors with different ring sizes and evaluated them in two solid tumor cell lines and one normal cell line. A seven membered ring compound, 17, was found to be the most potent with sub-micromolar IC_50s in breast (0.76 μM) and ovarian (0.76 μM) cancer cell lines. No significant H₂S release was detected in aqueous solution for this compound. However, confocal imaging showed that H₂S was released from 17 inside cells at a similar level to the widely studied H₂S donor GYY4137, which was shown to release 10 μM H₂S after 12 h at a concentration of 400 μM. Comparison of 17 with its non-sulfur oxygen analogue, 26, provided evidence that the sulfur atom is important for its potency. However, the significant potency observed for 26 (5.94–11.0 μM) indicates that the high potency of 17 is not entirely due to release of H₂S. Additional mechanism(s) appear to be responsible for the observed activity, hence more detailed studies are required to better understand the role of H₂S in cancer with potent thiophosphorus agents.     

Oxytocin (OT) and arginine-vasopressin (AVP) act on OT receptors and not AVP V1a receptors to enhance social recognition in adult Syrian hamsters (Mesocricetus auratus)

Social recognition is a fundamental requirement for all forms of social relationships. A majority of studies investigating the neural mechanisms underlying social recognition in rodents have investigated relatively neutral social stimuli such as juveniles or ovariectomized females over short time intervals (e.g., 2 h). The present study developed a new testing model to study social recognition among adult males using a potent social stimulus. Flank gland odors are used extensively in social communication in Syrian hamsters and convey important information such as dominance status. We found that the recognition of flank gland odors after a 3 min exposure lasted for at least 24 h, substantially longer than the recognition of other social cues in rats and mice. Intracerebroventricular injections of OT and AVP prolonged the recognition of flank gland odor for up to 48 h. Selective OTR but not V1aR agonists, mimicked these enhancing effects of OT and AVP. Similarly, selective OTR but not V1aR antagonists blocked recognition of the odors after 20 min. In contrast, the recognition of non-social stimuli was not blocked by either the OTR or the V1aR antagonists. Our findings suggest both OT and AVP enhance social recognition via acting on OTRs and not V1aRs and that the recognition enhancing effects of OT and AVP are limited to social stimuli.     

A short course of infusion of a hydrogen sulfide-donor attenuates endotoxemia induced organ injury via stimulation of anti-inflammatory pathways,with no additional protection from prolonged infusion

Organ failure is associated with increased mortality and morbidity in patients with systemic inflammatory response syndrome. Previously, we showed that a short course of infusion of a hydrogen sulfide (H₂S) donor reduced metabolism with concurrent reduction of lung injury. Here, we hypothesize that prolonged H₂S infusion is more protective than a short course in endotoxemia with organ failure. Also, as H₂S has both pro- and anti-inflammatory effects, we explored the effect of H₂S on interleukin production.Endotoxemia was induced by an intravenous bolus injection of LPS (7.5 mg/kg) in mechanically ventilated rats. H₂S donor NaHS (2 mg/kg) or vehicle (saline) was infused and organ injury was determined after either 4 or 8 h. A short course of H₂S infusion was associated with reduction of lung and kidney injury. Prolonged infusion did not enhance protection. Systemically, infusion of H₂S increased both the pro-inflammatory response during endotoxemia, as demonstrated by increased TNF-α levels, as well as the anti-inflammatory response, as demonstrated by increased IL-10 levels. In LPS-stimulated whole blood of healthy volunteers, co-incubation with H₂S had solely anti-inflammatory effects, resulting in decreased TNF-α levels and increased IL-10 levels. Co-incubation with a neutralizing IL-10 antibody partly abrogated the decrease in TNF-α levels. In conclusion, a short course of H₂S infusion reduced organ injury during endotoxemia, at least in part via upregulation of IL-10.     

Sulfate reduction from phosphogypsum using a mixed culture of sulfate-reducing bacteria

Phosphogypsum (CaSO₄), a primary by-product of phosphoric acid production, is accumulated in large stockpiles and occupies vast areas of land. It poses a severe threat to the quality of water and land in countries producing phosphoric acid. In this study, the potential of sulfate-reducing bacteria for biodegradation of this sulfur-rich industrial solid waste was assessed. The effect of phosphogypsum concentration, carbon and nitrogen sources, temperature, pH and stirring on the growth of sulfate-reducing bacteria was investigated. Growth of sulfate-reducing bacteria was monitored by measuring sulfide production. Phosphogypsum was shown to be a good source of sulfate, albeit that the addition of organic carbon was necessary for bacterial growth. Biogenic sulfide production occurred with phosphogypsum up to a concentration of 40 g L⁻¹, above which no growth of sulfate-reducing bacteria was observed. Optimal growth was obtained at 10 g L⁻¹ phosphogypsum. Both the gas mixture H₂/CO₂ and lactate supported high amounts of H₂S formation (19 and 11 mM, respectively). The best source of nitrogen for sulfate-reducing bacteria was yeast extract, followed by ammonium chloride. The presence of nitrate had an inhibitory effect on the process of sulfate reduction. Stirring the culture at 150 rpm slightly stimulated H₂S formation, probably by improving sulfate solubility.     

Syntheses,characterization, antimicrobial and cytotoxic activities of pyridine-2,5-dicarboxylate complexes with 1,10-phenanthroline

In this study, four mononuclear M(II)-pyridine-2,5-dicarboxylate (M = Co(II), Ni(II), Cu(II) and Zn(II) complexes with pyridine-2,5-dicarboxylic acid or isocinchomeronic acid, 1,10-phenanthroline (phen), [Co(Hpydc)₂(phen)]·H₂O (1), [Ni(pydc)(phen)₂]·6.5H₂O (2) [Cu(pydc)(phen)(H₂O)₂] (3) and [Zn(pydc)(phen)(H₂O)₂]·H₂O (4) have been synthesized. Elemental, thermal and mass analyses, molar conductance, magnetic susceptibilities, IR and UV/vis spectroscopic studies have been performed to characterize the complexes. Subsequently, these ligands and complexes were tested for antimicrobial activity by disc diffusion method on Gram positive, negative bacteria and yeast. In addition, cytotoxic activity tests were performed on rat glioma (C6) cells by MTT viability assay for 24 and 48 h. Antimicrobial activity results demonstrated that when compared to the standard antibiotics, phen displayed the most effective antimicrobial effect. The effect of synthesized complexes was close to phen or less. Cytotoxic activity results showed that IC₅₀ value of phen was determined as 31 μM for 48 h. (1) and (2) compared to the alone ligand had less toxic activity. IC₅₀ values of (3) for 24 and 48 h treatments were 2.5 and 0.6 μM, respectively. IC₅₀ value of (4) for 48 h was 15 μM. In conclusion, phen, (3) and (4) may be useful as antibacterial and antiproliferative agents in the future.     

Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung

Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure. Serum H₂S level and CSE protein expression in lung tissue were higher, by 2.04- and 2.33-fold, respectively, in CS-exposed rats than in controls (P < 0.05). Exogenous administration of NaHS to CS-exposed rats alleviated airway reactivity induced by acetylcholine (Ach) or potassium chloride (KCl) by 17.4% and 13.8%, respectively, decreased lung pathology score by 32.7%, inhibited IL-8 and TNF- α concentrations in lung tissue by 34.2% and 31.4%, respectively, as compared with CS-exposed rats (all P < 0.05). However, blocking endogenous CSE with PPG in CS-exposed rats increased airway reactivity induced by Ach or KCl, by 24.1% and 24.5%, respectively, and aggravated lung pathology score, by 44.8%, as compared with CS-exposed rats (all P < 0.01). Incubation in vitro with NaHS, 1–3 mmol/L, relaxed rat tracheal smooth muscle precontracted by Ach or KCl. However, the NaHS-induced relaxation was not blocked by glibenclamide (10^?4 mol/L), L-NAME (10^?4 mol/L), or ODQ (1 μmol/L) or denudation of epithelium. Endogenous H₂S may have a protective role of anti-inflammation and bronchodilation in chronic CS-induced pulmonary injury.     

Slow generation of hydrogen sulfide from sulfane sulfurs and NADH models

Here we report the model studies of the reactions between NADH models (using HEH and BNAH) and sulfane sulfurs (using polysulfides). Such reactions could lead to the oxidation of NADH models and the production of hydrogen sulfide (H₂S). Kinetics of the reaction between BNAH and elemental sulfur S₈ were determined in ethanol and the second-order rate constant was found to be 0.074 M^?1 min^?1 (at 37 °C) suggesting this is a slow process.     

Phenol and sulfide oxidation in a denitrifying biofilm reactor and its microbial community analysis

A microbial consortium attached onto a polyethylene support was used to evaluate the simultaneous oxidation of sulfide and phenol by denitrification. The phenol, sulfide and nitrate loading rates applied to an inverse fluidized bed reactor were up to 168 mg phenol–C/(l d), 37 mg S^2?/(l d) and 168 mg NO₃^?–N/(l d), respectively. Under steady state operation the consumption efficiencies of phenol, sulfide and nitrate were 100%. The N₂ yield (g N₂/g NO₃^?–N) was 0.89. The phenol was mineralized resulting in a yield of 0.82 g bicarbonate–C/g phenol–C and sulfide was completely oxidized to sulfate with a yield of 0.99 g SO₄^2?–S/g S^2?. 16S rRNA gene-based microbial community analysis of the denitrifying biofilm showed the presence of Thauera aromatica, Thiobacillus denitrificans, Thiobacillus sajanensis and Thiobacillus sp. This is the first work reporting the simultaneous oxidation of sulfide and phenol in a denitrifying biofilm reactor.     

Cystathionine γ lyase–hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes

Adipocytes express the cystathionine γ lyase (CSE)–hydrogen sulfide (H₂S) system. CSE–H₂S promotes adipogenesis but ameliorates adipocyte insulin resistance. We investigated the mechanism of how CSE–H₂S induces these paradoxical effects. First, we confirmed that an H₂S donor or CSE overexpression promoted adipocyte differentiation. Second, we found that H₂S donor inhibited but CSE inhibition increased phosphodiesterase (PDE) activity. H₂S replacing isobutylmethylxanthine in the differentiation program induced adipocyte differentiation in part. Inhibiting PDE activity by H₂S induced peroxisome proliferator activated receptor γ (PPARγ) protein and mRNA expression. Of note, H₂S directly sulfhydrated PPARγ protein. Sulfhydrated PPARγ increased its nuclear accumulation, DNA binding activity and adipogenesis gene expression, thereby increasing glucose uptake and lipid storage, which were blocked by the desulfhydration reagent DTT. H₂S induced PPARγ sulfhydration, which was blocked by mutation of the C139 site of PPARγ. In mice fed a high-fat diet (HFD) for 4 weeks, the CSE inhibitor decreased but H₂S donor increased adipocyte numbers. In obese mice fed an HFD for 13 weeks, H₂S treatment increased PPARγ sulfhydration in adipose tissues and attenuated insulin resistance but did not increase obesity. In conclusion, CSE–H₂S increased PPARγ activity by direct sulfhydration at the C139 site, thereby changing glucose into triglyceride storage in adipocytes. CSE–H₂S-mediated PPARγ activation might be a new therapeutic target for diabetes associated with obesity.     

Increased thirst and vasopressin secretion after myocardial infarction in rats

Impaired regulation of salt and water balance in left ventricular dysfunction and heart failure can lead to pulmonary and peripheral edema and hyponatremia. Previous studies of disordered water regulation in heart failure have used models of low cardiac output with normal cardiac function (e.g., inferior vena cava ligation). We investigated thirst and vasopressin (AVP) secretion in a rat myocardial infarction model of chronic left ventricular dysfunction/heart failure in response to a 24-h water deprivation period. Thirst (implied from water drunk), hematocrit, plasma renin activity, and plasma AVP concentrations increased with water deprivation vs. ad libitum water access. Thirst and plasma AVP concentrations were significantly positively correlated with infarct size after 24-h water deprivation but not under ad libitum water access conditions. The mechanism by which this occurs is unclear but could involve increased osmoreceptor sensitivity, altered stimulation of baroreceptors, the renin-angiotensin system, or altered central neural control.     

Toxicity of basil and orange essential oils and their components against two coleopteran stored products insect pests

Two commercialized essential oils and their constituent compounds were investigated for fumigant and contact activities against two grain storage insects, adults of the maize weevil (Sitophilus zeamais) and the red flour beetle (Tribolium castaneum). The two commercialized basil and orange oils showed strong fumigant and contact activities against S. zeamais and T. castaneum. The constituents of the basil oil were linalool (21.83%), estragole (74.29%), and α-humulene (2.17%), and those of the orange oil were α-pinene (0.54%), sabinene (0.38%), β-myrcene (1.98%), limonene (96.5%), and linalool (0.6%). As a toxic fumigant, the basil oil was more effective (24-h LC₅₀ = 0.014 and 0.020 mg cm^− 3) than the orange oil (24-h LC₅₀ = 0.106 and 0.130 mg cm^− 3) against S. zeamais and T. castaneum adults, respectively. Among the constituents of the two essential oils, the toxicity of estragole was the highest (0.004 and 0.013), followed by linalool (0.016 and 0.023), limonene (0.122 and 0.171), α-pinene (0.264 and 0.273), and β-myrcene (0.274 and 0.275) based on 24-h LC₅₀ values (mg cm^− 3). Similar results were obtained in a contact toxicity test. The contact activity of basil oil was more toxic than orange oil, and estragole and linalool showed pronounced contact toxicity against S. zeamais and T. castaneum adults. Alpha-humulene had no activity as a fumigant at the tested doses, but it did have an effect as a contact poison, having 24-h LD₅₀ values of 0.040 and 0.045 mg adult^− 1 to S. zeamais and T. castaneum, respectively. Although basil oil, orange oil, and their components displayed both contact and fumigant toxicities, their effects were mainly exerted by fumigant action via the vapor phase. Thus, basil oil, orange oil, and their components could be potential candidates as new fumigants for the control of S. zeamais and T. castaneum adults.     

Exercise modulates the aortic renin-angiotensin system independently of estrogen therapy in ovariectomized hypertensive rats

The renin-angiotensin-system is an important component of cardiovascular control and is up-regulated under various conditions, including hypertension and menopause. The aim of this study was to evaluate the effects of swimming training and estrogen therapy (ET) on angiotensin-II (ANG II)-induced vasoconstriction and angiotensin-(1-7) [ANG-(1-7)]-induced vasorelaxation in aortic rings from ovariectomized spontaneously hypertensive rats. Animals were divided into Sham (SH), Ovariectomized (OVX), Ovariectomized treated with E2 (OE2), Ovariectomized plus swimming (OSW) and Ovariectomized treated with E2 plus swimming (OE2 + SW) groups. ET entailed the administration of 5 μg of 17β-Estradiol three times per week. Swimming was undertaken for sixty minutes each day, five times per week. Both, training and ET were initiated seven days following ovariectomy. Forty-eight hours after the last treatment or training session, the animals’ systolic blood pressures were measured, and blood samples were collected to measure plasma ANG II and ANG-(1-7) levels via radioimmunoassay. In aortic rings, the vascular reactivity to ANG II and ANG-(1-7) was assessed. Expression of ANG-(1-7) in aortic wall was analyzed by immunohistochemistry. The results showed that both exercise and ET increased plasma ANG II levels despite attenuating systolic blood pressure. Ovariectomy increased constrictor responses to ANG II and decreased dilatory responses to ANG-(1-7), which were reversed by swimming independently of ET. Moreover, it was observed an apparent increase in ANG-(1-7) content in the aorta of the groups subjected to training and ET. Exercise training may play a cardioprotective role independently of ET and may be an alternative to ET in hypertensive postmenopausal women.     

Central effects of angiotensin II in conscious hamsters: drinking,pressor response,and release of vasopressin

Summary The effects of intracerebroventricular (icv) injections of angiotensin II (ANG II) on water intake, blood pressure, heart rate, and plasma arginine-vasopressin (AVP) concentration were studied in chronically instrumented adult male Syrian golden hamsters (Mesocricetus auratus). Furthermore, the effects of pharmacological ganglionic blockade, and of vascular AVP receptor blockade, on central ANG II-induced cardiovascular responses were investigated. ANG II (1, 10, and 100 ng, icv) elicited dose-dependent increases in water intake and arterial blood pressure. Heart rate showed a biphasic response with a short initial non dose-dependent tachycardic and a subsequent longer lasting bradycardic phase. Plasma AVP concentration was increased two and a half fold with 100 ng ANG II icv. Both ganglionic blockade and vascular AVP receptor blockade significantly attenuated the central ANG II-induced pressor response. The tachycardic phase of the heart rate response was abolished by ganglionic blockade and the bradycardic phase was significantly diminished by AVP receptor blockade. The results support the hypothesis that brain ANG II may participate in the central control of body fluid volume and in central cardiovascular regulation in conscious hamsters.