Can Acupuncture be a Part of the Treatment for Breast Cancer-Related Lymphedema? A Systematic Review of the Safety and Proposed Model for Care.

Acupuncture is a potential therapy for breast cancer-related lymphedema (BCRL). Despite a recent meta-analysis on efficacy, data on acupuncture safety in BCRL are lacking. Current clinical guidelines recommend avoiding needling in the upper extremity affected by lymph node dissection. We undertook a systematic review focusing on acupuncture safety and treatment protocols in clinical trials for BCRL. Literature searches were conducted in PubMed, Ovid, CINAHL, and Cochrane library. Eight clinical trials on acupuncture for BCRL were analyzed. The Standards of Acupuncture intervention (STRICTA 2010) and Cochrane risk of bias (RoB2 2019) were applied to assess methods for acupuncture interventions within Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Quantity and severity of adverse events (AE) were reviewed. A total of 189 subjects participated in 8 clinical trials with 2965 acupuncture treatments. No serious adverse events (SAE) were reported regardless of treatment laterality or protocol, with only a single grade 2 skin infection in 2,965 total treatments (0.034%), including 1,165 bilateral and 225 ipsilateral treatments. Our comprehensive review of clinical trials of acupuncture for BCRL demonstrated no significant adverse events in 2,965 treatments, including 1,390 in the affected limb. An approach for routine integration of acupuncture into BCRL maintenance therapy is proposed.

Effects of supplemental lysine and methionine with zilpaterol hydrochloride on feedlot performance, carcass merit, and skeletal muscle fiber characteristics in finishing feedlot cattle.

Feeding zilpaterol hydrochloride (ZH) with ruminally protected AA was evaluated in a small-pen feeding trial. Crossbred steers ( = 180; initial BW = 366 kg) were blocked by weight and then randomly assigned to treatments (45 pens; 9 pens/treatment). Treatment groups consisted of no ZH and no AA (Cont-), ZH and no AA (Cont+), ZH and a ruminally protected lysine supplement (Lys), ZH and a ruminally protected methionine supplement (Met), and ZH and ruminally protected lysine and methionine (Lys+Met). Zilpaterol hydrochloride (8.3 mg/kg DM) was fed for the last 20 d of the finishing period with a 3-d withdrawal period. Lysine and Met were top dressed daily for the 134-d feeding trial to provide 12 or 4 g·hd·d, respectively, to the small intestine. Carcass characteristics, striploins, and prerigor muscle samples were collected following harvest at a commercial facility. Steaks from each steer were aged for 7, 14, 21, and 28 d, and Warner-Bratzler shear force (WBSF) was determined as an indicator of tenderness. Prerigor muscle samples were used for immunohistological analysis. Cattle treated with Met and Lys+Met had increased final BW ( < 0.3) and ADG ( < 0.05) compared to Cont- and Cont+. Supplementation of Lys, Met, and Lys+Met improved G:F ( < 0.05) compared to Cont- during the ZH feeding period (d 111 to 134) as well as the entire feeding period ( < 0.05). Zilpaterol hydrochloride increased carcass ADG ( < 0.05) when compared to non-ZH-fed steers. Methionine and Lys+Met treatments had heavier HCW ( < 0.02) than that of Cont-. Yield grade was decreased ( < 0.04) for Cont+ steers compared to steers treated with Lys, Lys+Met, and Cont-. Tenderness was reduced ( < 0.05) with ZH regardless of AA supplementation. Lysine, Met, Lys+Met, and Cont+ had less tender steaks ( < 0.05) throughout all aging groups compared to Cont-. Steaks from Lys-treated steers were less tender ( < 0.05) than those of Cont+ during the 7- and 14-d aging periods. Nuclei density was the greatest with Cont- cattle compared to all other treatments suggesting a dilution effect of the nuclei in the larger muscle fibers with ZH feeding. Supplementation of Met in conjunction with ZH feeding increased ADG and HCW although this may lead to decreased tenderness even after aging for 28 d. These findings indicated that steers fed ZH may require additional AA absorbed from the small intestine to maximize performance.

Increased metabolic rate and insulin sensitivity in male mice lacking the carcino-embryonic antigen-related cell adhesion molecule 2.

AIMS/HYPOTHESIS: The carcino-embryonic antigen-related cell adhesion molecule (CEACAM)2 is produced in many feeding control centres in the brain, but not in peripheral insulin-targeted tissues. Global Ceacam2 null mutation causes insulin resistance and obesity resulting from hyperphagia and hypometabolism in female Ceacam2 homozygous null mutant mice (Cc2 [also known as Ceacam2](-/-)) mice. Because male mice are not obese, the current study examined their metabolic phenotype. METHODS: The phenotype of male Cc2(-/-) mice was characterised by body fat composition, indirect calorimetry, hyperinsulinaemic-euglycaemic clamp analysis and direct recording of sympathetic nerve activity. RESULTS: Despite hyperphagia, total fat mass was reduced, owing to the hypermetabolic state in male Cc2(-/-) mice. In contrast to females, male mice also exhibited insulin sensitivity with elevated ß-oxidation in skeletal muscle, which is likely to offset the effects of increased food intake. Males and females had increased brown adipogenesis. However, only males had increased activation of sympathetic tone regulation of adipose tissue and increased spontaneous activity. The mechanisms underlying sexual dimorphism in energy balance with the loss of Ceacam2 remain unknown. CONCLUSIONS/INTERPRETATION: These studies identified a novel role for CEACAM2 in the regulation of metabolic rate and insulin sensitivity via effects on brown adipogenesis, sympathetic nervous outflow to brown adipose tissue, spontaneous activity and energy expenditure in skeletal muscle.

Micronucleus assays with Tradescantia pollen tetrads: an update.

Micronucleus (MN) assays with early pollen tetrad cells of Tradescantia (Trad-MN assays) are at present the most widely used bioassays with plants for the detection of genotoxins in the environment. So far, ∼ 160 chemicals have been tested and ∼ 100 articles that concern complex environmental mixtures were published. This article summarises the results of Trad-MN studies, which have been carried out during the last 15 years with individual compounds and investigations concerning the pollution of environmental compartments (soil, water and air). The evaluation shows that the effects of certain genotoxins such as heavy metals, radionuclides, pesticides and air pollutants can be easily detected with this test. Comparisons with results obtained in MN studies with mitotic (root tip) cells indicate that meiotic tetrad cells are in general more sensitive. Important issues for future research concern the evaluation of the suitability of wildlife Tradescantia species that are sometimes used instead of specific clones (such as #4430 for which standardised protocols have been developed) as well as the assessment of the predictive value of Trad-MN results in regard to the prediction of cancer hazards in humans and adverse effects at the ecosystem level. The fact that the genotoxic effects of certain compound such as metals, which can be detected with plant bioassays, in particular with the Trad-MN assay but not in other commonly used bioassays (e.g. in bacterial tests) makes them an essential element in the batteries for environmental monitoring.

Roasted licorice extracts dampen high glucose-induced mesangial hyperplasia and matrix deposition through blocking Akt activation and TGF-beta signaling.

Diabetic nephropathy (DN) characterized as nephrotic syndrome and diffuse glomerulosclerosis can cause renal failure and end-stage kidney disease. Expansion of mesangial matrix around capillaries in the kidney glomeruli is a prominent feature of DN. This study investigated whether licorice extracts inhibited mesangial cell (MC) proliferation and matrix accumulation induced by high glucose (HG). Human renal MC were cultured in media containing 5.5 mM glucose plus 27.5 mM mannitol as an osmotic control or 33 mM glucose for 3 d in the presence of water or ethanol extracts from raw licorice (LW, LE) or roasted licorice (RLW, RLE). Non-polar components including glycyrrhetic acid were elevated during licorice roasting, whereas polar components soluble in water extracts were diminished. Exposure of cells to HG caused significant increases in collagen IV secretion and connective tissue growth factor (CTGF) expression, which was appeased by RLW and RLE at transcriptional levels. The inhibitory potency was high in the order of RLE > or = RLW > or = LE > > LW. Non-polar glycyrrhetic acid but not glycyrrhizin retarded HG-stimulated mesangial matrix deposition through diminishing CTGF expression. In addition, RLW and RLE but not LW modulated membrane type matrix metalloproteinase-1 (MT-1 MMP) expression, MMP-2 activity and tissue inhibitor of MMP-2 (TIMP-2), which facilitated the degradation of mesangial matrix. Furthermore, the augmented expression of CTGF and TIMP-2 in HG-exposed cells was mediated by Akt activation and TGF-beta/Smad signaling through PKCbeta2-responsive signaling pathways. However, HG-down-regulated MT-1 MMP expression was independent of activation of ERK1/2 and Akt when using their inhibitors of DB98059 (ERK1/2) and LY294002 (Akt) alone or in combination. These results demonstrate that extracts from roasted licorice may be highly potent therapeutic agents for the prevention and treatment of mesangial fibrosis and glomerulosclerosis leading to diabetes nephropathy due to longstanding diabetes mellitus.

Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii.

BACKGROUND: Celastrol, a quinone methide triterpenoid isolated from the Celastraceae family, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation. MATERIALS AND METHODS: Anti-inflammatory effects of celastrol (0-1 microM) were examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. To investigate the effects of celastrol (0-50 microg per mice) in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse ear oedema model. RESULTS: Our in vitro experiments showed that celastrol suppressed not only LPS-stimulated generation of nitric oxide and prostaglandin E(2), but also expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW264.7 cells. Similarly, celastrol inhibited LPS-induced production of inflammatory cytokines, including tumour necrosis factor-alpha and interleukin-6. In an animal model, celastrol protected mice from TPA-induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines. CONCLUSIONS: Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases.

Effects of oral epigallocatechin gallate supplementation on the minimal erythema dose and UV-induced skin damage.

BACKGROUND/AIMS: Excessive exposure to UV radiation causes acute adverse effects like sunburn and photosensitivity reactions and is involved in the induction and development of skin cancer. It has been reported that antioxidants have photoprotective effects against solar UV radiation. We investigated the effect of oral epigallocatechin gallate (EGCG), a powerful antioxidant in green tea, on the minimal erythema dose (MED) and UV-induced skin damage. METHOD: Female HWY/Slc hairless rats were fed the normal diet supplemented with 1,500 ppm EGCG for 8 weeks; then, the MED was determined and visual scores and transepidermal water loss were assessed to evaluate the severity of UV-induced skin damage. RESULTS: At week 8 of the study, the use of dietary EGCG significantly increased MED. UV-radiation-induced sunburn severity and alterations in epidermal barrier function were also attenuated by the supplementation of EGCG. CONCLUSION: Regular intake of EGCG strengthens the skin's tolerance by increasing MED and thus prevents UV-induced perturbation of epidermal barrier function and skin damage. These results suggest that EGCG is a potent candidate for systemic photoprotection.

The development of a novel cooking method (alternate roasting with its own fat) for chicken to improve nutritional value.

The goal of this study was to develop a novel cooking method for fried meat products, to improve their nutritional value, and to provide superior taste and texture. We used the fat derived from each individual meat source during radiant heat roasting (alternate roasting with its own fat: AROF) without deep-fat frying (DFF), first without any air flow and subsequently with an exposure to air flow. We then compared these roasted chicken samples to breaded fried chicken samples that were deep-fat fried in 3 types of fat: soybean oil (SB), partially hydrogenated soybean oil (PSB), and lard. The final fat contents of both the skin and lean parts of the AROF samples of chicken were less than half of those of the DFF groups. The total trans-fatty acids (TFA) contents were significantly lower in the AROF samples compared to the DFF samples. The cholesterol levels of the samples did not show any significant differences among the tested groups, except for the sample fried in lard, which was significantly higher. Moreover, the sensory evaluation results showed that the crispy texture of the AROF samples was not significantly different from that of the DFF samples (P < 0.05); the AROF samples had higher scores for the characteristic fried flavor and for overall acceptability (P < 0.05). This study shows the potential value of products prepared by AROF, which can successfully replace DFF methods used for chicken and other meat products and improve their nutritional value.

Glabridin, a functional compound of liquorice, attenuates colonic inflammation in mice with dextran sulphate sodium-induced colitis.

Inflammatory bowel disease (IBD) is characterized by detrimental immune reactivity in the gut, and the imbalance between proinflammatory and anti-inflammatory reactivity. The aims of this study were to determine whether oral administration of glabridin, a functional component of liquorice, could ameliorate dextran sulphate sodium (DSS)-induced colitis, as well as to understand the possible underlying mechanisms. Acute experimental colitis was induced in BALB/c mice by treatment with 5% DSS for 7 days. Glabridin (10 or 50 mg/kg/day) was given for 7 days. Treatment with glabridin significantly attenuated mortality, loss of body weight, shortening of the colon and severe clinical symptoms. This was associated with a remarkable amelioration of the disruption of the colonic architecture, a significant reduction in colonic myeloperoxidase (MPO) activity and the production of inflammatory mediators such as nitric oxide (NO), prostaglandin (PG) E2, and proinflammatory cytokines. These results suggest that glabridin-mediated anti-inflammatory action on colorectal sites may be a useful therapeutic approach to IBD.

Investigation of the generation of hydroxyl radicals and their oxidative role in the presence of heterogeneous copper catalysts.

The presence and impact of hydroxyl radicals generated via the catalytic decomposition of H(2)O(2) over heterogeneous copper catalysts were investigated by using two detection methods, an electron spin resonance-spin trapping method and a chemical probe method. Detection of the (5,5-dimethyl-1-pyrroline-N-oxide)-OH adduct signal and formation of 4-chlorocatechol during the oxidation of a 4-chlorophenol substrate demonstrated that the three heterogeneous copper catalysts employed here (CuO, Cu/Al(2)O(3) and CuO.ZnO/Al(2)O(3)) were capable of generating hydroxyl radicals in combination with H(2)O(2). The oxidative mechanism of the hydroxyl radical in the presence of heterogeneous copper catalysts is discussed with regard to the further oxidation of the (5,5-dimethyl-1-pyrroline-N-oxide)-OH adduct and hydroxylated products of 4-chlorophenol oxidation. Interestingly, integration of the 5,5-dimethyl-1-pyrroline-N-oxide-OH adduct signal could not be used to reliably measure the total amount of hydroxyl radicals generated as a result of oxidative attack on the adduct. This may be as a result of locally higher hydroxyl radical concentrations in the presence of a heterogeneous catalyst leading to further unwanted oxidation of the (5,5-dimethyl-1-pyrroline-N-oxide)-OH.

Subacute toxicity evaluation of a new camptothecin anticancer agent CKD-602 administered by intravenous injection to rats.

The subacute toxicity of a new camptothecin anticancer agent, CKD-602, was investigated after 4-week repeated intravenous administration of the chemical in Sprague-Dawley rats. The test chemical was administered intravenously to rats at dose levels of 0, 0.003, 0.013, or 0.067 mg/kg/day for males and 0, 0.004, 0.018, or 0.089 mg/kg/day for females. At the end of the treatment period, 10 rats/sex/group were sacrificed. The remaining 5 rats/sex in the vehicle control and high dose groups continued the study without treatment for 2 weeks (recovery period). During the test period, clinical signs, mortality, body weights, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross findings, organ weights, and histopathology were examined. In both sexes of the high dose group, an increase in the incidence of abnormal clinical signs and paleness of the eyes, a reduction in the body weight gain, food consumption and urine protein, and an increase in the water consumption were observed. Hematological investigations revealed a decrease in the red blood cells, hemoglobin and hematocrit and an increase in the mean corpuscular volume, mean corpuscular hemoglobin, platelets, and reticulocytes in a dose-dependent manner. Serum total cholesterol and total protein values were lower in females than those of controls, but not in males. An increase in the heart and liver weights and a decrease in the thymus weight were also found. Histopathological alterations included an increase in the incidence of atrophy of the sternal marrow, atrophy, fibrosis and mast cell hyperplasia of the femoral marrow, atrophy of the white pulp and extramedullary hematopoiesis of the spleen, atrophy of the thymus, auricular hypertrophy of the heart, extramedullary hematopoiesis and centriacinar telangiectasis of the liver, follicular degeneration of the ovary, and inflammation of the tail. The major treatment-related effects were not recovered at the end of 2-week recovery period. There were no adverse effects in the low and middle dose groups of both genders. In the present experimental conditions, the target organs were determined to be bone marrow, blood cells, spleen, liver, thymus, and heart. The no-observed-adverse-effect level was considered to be 0.013 mg/kg/day for males and 0.018 mg/kg/day for females.

Some general regularities of synergistic interaction of hyperthermia with various physical and chemical inactivating agents.

Various cellular systems have been analysed for synergistic interactions of the simultaneous action of hyperthermia with physical agents including ionizing radiation, ultraviolet light, and ultrasound, and with chemical agents including thio-TEPA and cis-DDP. Some general rules of synergistic interaction were revealed. First, for every constant rate or intensity of exposure to physical factors or concentration of chemical agents, synergy can be observed only within a certain temperature range that is different for various cellular systems. Secondly, within this range, there is a specific temperature that maximizes the synergistic effect. Any deviation of temperature from the optimal one results in a reduction in synergy. Thirdly, the rate of exposure to physical agents or the concentration of chemical agents strongly influences the synergy; i.e. as the dose rate or concentration is reduced, the temperature for maximum synergism decreases. Possible interpretations of the mechanisms responsible for these relationships of synergy are discussed.

Ovarian expression of melatonin Mel(1a) receptor mRNA during mouse development.

Melatonin, secreted by the pineal gland, is involved in the regulation of many physiological functions of various species of animals. In the present study, the expression of gene for melatonin Mel(1a) receptor (MelR) was evaluated in the ovary, hypothalamus, and pituitary according to the developmental stages in female mice. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) and in situ PCR techniques were applied. According to the developmental stages, gene for MelR was differently expressed on ovary, hypothalamus, and pituitary. MelR gene was first expressed on pituitary prior to the expression in hypothalamus and ovary. Ovarian MelR gene started to express at birth. Unlike hypothalamic expression of MelR gene which was identified after birth, in pituitary, it was expressed at 16 days post coitum. In the ovary, the expression signal of MelR gene was identified on granulosa cells. However, the signal was not detected in the theca cells. It was weak in the primordial and atretic follicles. Taken together, it can be considered that melatonin has a pivotal role in the folliculogenesis.

2,2-Dimethyl-4,5-diaryl-3(2H)furanone derivatives as selective cyclo-oxygenase-2 inhibitors.

A series of 2,2-dimethyl-5-[4-(methylsulfonyl)phenyl]-4-phenyl-3(2H)furanones was prepared and evaluated for their ability to inhibit cyclo-oxygenase-2 (COX-2).

Immune-stimulating properties of polysaccharides from Phellodendri cortex (Hwangbek).

Heteropolysaccarides were isolated from the Korean medicinal plant, Phellodendri cortex (Hwangbek), by hot water and alkali extractions. The extracted polysaccharides were fractionated into eight fractions and they are mainly composed of D-N-acetylglucosamine, D-galactose, D-mannose, and D-glucose. Among the polysaccharide fractions, Fr.-2 showed a potent B-lymphocyte-stimulating activity in a system using polyclonal antibody forming cells in C57BL/6XC3H mice at dosages of 2-10 mg. On the basis of their solubility in aqueous ethanol, four fractions of Fr.-2-1 to Fr.-2-4 were further obtained from the Fr.-2, and Fr.-2-3 was divided into Fr.-2-3-1, 2, 3, and 4 by DEAE cellulose chromatography. The main activity was found in Fr.-2-3-2, which contained 100% (w/w) of carbohydrates and further purified to Fr.-2-3-2-2 by gel filtration chromatography using TSK Gel HW50S. Fr.-2-3-2-2, having a molecular weight of about 230 kDa, showed the highest B-cell-stimulating activity and the half-maximal concentration for B-lymphocyte-stimulating activity was ca. 2.2 microg/ml.

Nucleotide sequence analysis of the 3'-terminal region of two Korean isolates of lily symptomless Carlavirus and expression of the coat protein in E. coli.

The 3'-terminal regions of the genomic RNAs of two Korean isolates of the lily symptomless Carlavirus (LSV), LSV-Ko and LSV-KII, were cloned and their nucleotide sequences were determined. The nucleotide sequence analysis and protein analysis by the Western blot revealed that E. coli expressed a 32-kDa protein that is the viral coat protein (CP) for the LSV. The two Korean strains share 98.4% and 98.3% sequence identities at the nucleotide and amino acid levels, respectively. The CP gene of LSV-Ko showed 99.1% and 87.0% nucleotide sequence identities, and 99.0% and 96.6% amino acid sequence identities with those of the Netherlands and the Japanese LSV strains, respectively. A pairwise amino acid sequence comparison revealed a sequence similarity of 29.6% to 69.8% between LSV-Ko and other species of the carlavirus. The 16 kDa protein of LSV-Ko shares 17.6% to 42.7% amino acid similarity with those of 8 other the carlaviruses, and they are variable in the N-terminal region. The Cys repeated zinc finger nucleic acid binding domain was found in the 16 kDa protein for all of the LSV strains. Sequence comparisons of the 7 kDa protein of LSV in the strain level showed significant identities from 100.0% to 98.4%. LSV-Ko shares 21.9% to 42.2% amino acid similarity with those of 8 other carlaviruses, 4 members of the potexviruses, and a closterovirus. LSV is closely related to blueberry scorch virus (BISV) based upon the phylogenetic tree analyses of the three proteins, indicating LSV to be a quite distinct member of the genus Carlavirus.

Antitumor activity of the aqueous-alcoholic extracts from unripe cotton ball of Gossypium indicum.

The present study investigated the antitumor activity of the aqueous-alcoholic extracts from unripe cotton balls of Gossypium indicum. An Exposure of murine B16 melanoma and L1210 lymphoma cells to the extracts resulted in their severe deaths in time- and concentration-dependent manners. Of the extracts, hydrophilic fractions were most efficacious for the antitumor activity and found to contain certain amounts of catechin and its derivatives. The hydrophilic extract fraction C36B2-8 had approximately 10 times more cytotoxic effects on B12 and L1210 cells than on isolated murine thymocytes. High concentrations (> 150 micrograms/ml) of C 36B3-8 mainly induced necrotic cell death. At low concentrations (< 100 micrograms/ml), however, C 36B3-8 induced not only necrosis but also apoptosis of the two tumor cell lines, which was proved by the TUNEL staining and DNA fragmentation techniques. The data indicate that certain ingredients of the cotton ball extract of G. indicum have an antitumor activity.

Renal angiomyolipoma: selective arterial embolization--effectiveness and changes in angiomyogenic components in long-term follow-up.

PURPOSE: To evaluate the efficacy of selective arterial embolization in symptomatic renal angiomyolipoma (AML) and the change in angiomyogenic components during long-term follow-up after embolization. MATERIALS AND METHODS: Fourteen adult patients with symptomatic AMLs underwent 16 selective arterial embolizations. The embolic materials used were absolute alcohol with (n = 5) or without (n = 3) iodized oil, Gianturco coils (n = 4), and polyvinyl alcohol foam powder with gelatin sponge (n = 2). Follow-up ultrasonography and computed tomography (CT) were performed in six and 14 patients, respectively. The effectiveness of selective arterial embolization was evaluated on the basis of the area of the angiomyogenic components in the AML on initial and follow-up images and clinical improvement. RESULTS: All patients showed devascularization of the tumor on the postembolization angiograms. In 13 patients, clinical symptoms disappeared. The follow-up period was 7-72 months (mean, 33 months). One patient underwent nephrectomy at 7 months after embolization because of a large cystic lesion found at 1 month. In long-term CT follow-up (> or =12 months) in 12 patients, nearly all angiomyogenic components disappeared, but fatty components partially shrank with liquefactive necrosis in tumors. CONCLUSION: Selective arterial embolization is an effective and safe treatment of AML. The angiomyomatous components crucial for the prevention of bleeding were very sensitive to the embolization.

Upregulation of endothelial and neuronal constitutive nitric oxide synthase in pregnant rats.

Pregnancy is characterized by hemodynamic and body fluid alterations. Increased nitric oxide (NO) production has been suggested to play a role in the hemodynamic alterations of pregnancy and has also been reported to increase arginine vasopressin (AVP) release. We therefore hypothesized that gestation could increase both NO synthase (NOS) constitutive isoforms, neuronal NOS and endothelial NOS, and thereby contribute to the hyposmolality and peripheral arterial vasodilation of pregnancy, respectively. The present study was therefore undertaken to examine the constitutive NOS isoforms in aortas, mesenteric arteries, and hypothalami of pregnant rats on day 20 of gestation compared with age-matched nonpregnant rats. Plasma AVP was determined by radioimmunoassay and hypothalamic mRNA AVP by solution hybridization assay. Hypothalamic neuronal NOS was assessed by Northern blot and Western blot; endothelial NOS was assessed by Western blot in arteries and hypothalamus. The results demonstrated that 1) plasma AVP and hypothalamic AVP mRNA are increased in pregnant rats (n = 8), 2) neuronal NOS protein and mRNA are increased in hypothalamus of pregnant rats (n = 4), and 3) endothelial NOS expression, as assessed by Western blot analysis, is increased in both conductance (aorta) as well as resistance (mesenteric) arteries of pregnant rats (n = 4). We conclude that both of the constitutive NOS isoforms are increased in pregnant rats, suggesting that the peripheral arterial vasodilation and hyposmolality of pregnancy could be mediated by these isoforms.