The effect of gestation and fetal mismatching on the development of autoimmune diabetes in non-obese diabetic mice

The impact of gestation and fetal-maternal interactions on pre-existent autoimmune beta cell destruction is widely unknown. The aim of this study was to investigate the influence of gestation per se and fetal mismatching on the onset of autoimmune diabetes in female non-obese diabetic (NOD) mice. We examined cumulative diabetes frequencies of NOD dams mated to syngeneic NOD, haploidentical CByB6F1/J and fully mismatched C57BL/6J male mice. Pregnancy from NOD males neither increased nor accelerated the diabetes onset of NOD dams (71% by age 28 weeks) compared to unmated female NOD mice (81% by age 28 weeks; P = 0·38). In contrast, delayed diabetes onset was observed when NOD dams were mated at 10 weeks of age with major histocompatibility complex (MHC) haploidentical CByB6F1/J male mice (38% at age 28 weeks; P = 0·01). Mating with fully MHC mismatched C57BL/6J male mice (72% diabetes by age 28 weeks; P = 0·22) or mating with the haploidentical males at the later time-point of age 13 weeks (64% versus 91% in unmated litter-matched controls; P = 0·13) did not delay diabetes significantly in NOD females. Because infusion of haploidentical male mouse splenocytes was found previously to prevent diabetes in NOD mice we looked for, but found no evidence of, persistent chimeric lymphocytes from haploidentical paternal origin within the dams' splenocytes. Gestation per se appears to have no aggravating or ameliorating effects on pre-existent autoimmune beta cell destruction, but pregnancy from MHC partially mismatched males delays diabetes onset in female NOD mice.     

A serial study of fluid balance during pregnancy,lactation and anestrus in goats

Water and salt balance was studied in the same goats during pregnancy, lactation and anestrus. All goats increased their water intake during the course of pregnancy, but individual differences were large. In general, twin pregnant (TP) goats drank more water than single pregnant (SP) animals (3.4±0.4; N=11 as compared to 2.5±0.3 litres/day; N=5) during the last weeks of pregnancy. During lactation the high water intake of TP goats persisted and the SP animals increased their intake to the same level as the TP goats. The water intake was reduced to about 2 1/day in both categories of animals during anestrus. Urine volume largely followed the changes in water intake in the individual animal. A continuous decrease in urine osmolality during the course of pregnancy occurred, but during lactation urine osmolality increased towards anestrus levels. TP goats generally retained more sodium than SP animals during pregnancy and during anestrus, whereas the figures were similar during lactation. Plasma Na, K and osmolality remained unchanged during pregnancy, lactation and anestrus, but a large fall in total plasma proteins and a moderate fall in hematocrit were observed during the course of pregnancy. Glomerular filtration rate of TP goats was elevated by about 35% during the 4th month of pregnancy, but did not differ from anestrus levels during the 3rd and 5th month or during lactation. Effective renal plasma flow was highest during the 3rd pregnancy month and then fell to reach lactation and anestrus levels during the 4th month of pregnancy. A few hours before parturition the animals became markedly dehydrated as shown by sudden increases in plasma Na, K, osmolality, total proteins and hematocrit. This water deficit was replenished within 26 h post-partum.     

SPARC在db/db小鼠肾脏组织中高表达

目的 检测db/db鼠肾脏组织中的富含半胱氨酸的酸性分泌蛋白(SPARC)的表达情况.方法 RT-PCR、Western blot及免疫荧光方法检测db/db鼠肾脏组织中的SPARC mRNA及蛋白的表达.结果 SPARC在db/db鼠肾脏组织中呈现高表达.结论 db/db鼠肾脏组织中的SPARC呈现高表达(P＜0.05),可能与糖尿病肾病的发生与发展有关.     

Pregnancy and lactation in the obese rat: Effects on maternal and pup weights

Lister hooded female rats, fed palatable high energy foods and chow, weighed significantly more than chow-fed control rats before mating. A smaller proportion of the obese rats became pregnant, and they lost more litters in lactation. When litters survived (7±1 pups), maternal weight changes differed between groups during lactation. The controls gained 6.2±3.2 g, whereas the obese rats lost variable amounts of weight despite the continued availability of the palatable diet. The rats that were heaviest at mating and parturition and which showed the largest non-fetal weight gains in pregnancy (i.e., the “large weight loss group”) lost 60.6±4.8 g, while less obese rats which showed similar non-fetal gains to controls (i.e., the “small weight loss group”) lost 24.6±3.2 g. Thus the weights of all groups converged and were similar after three weeks of lactation, but diverged again after weaning. During lactation the total energy intakes and amounts of protein consumed by the obese rats were significantly below those of controls, and total fat intake was significantly elevated. Although litter size and pup weights did not differ significantly at birth, pups of obese mothers weighed significantly less than those of controls at weaning. Maternal obesity in lactation appears to influence both body weight regulation and lactational performance.     

Telemedicine Technologies for Diabetes in Pregnancy: A Systematic Review and Meta-Analysis

BackgroundDiabetes in pregnancy is a global problem. Technological innovations present exciting opportunities for novel approaches to improve clinical care delivery for gestational and other forms of diabetes in pregnancy.ObjectiveTo perform an updated and comprehensive systematic review and meta-analysis of the literature to determine whether telemedicine solutions offer any advantages compared with the standard care for women with diabetes in pregnancy.MethodsThe review was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Randomized controlled trials (RCT) in women with diabetes in pregnancy that compared telemedicine blood glucose monitoring with the standard care were identified. Searches were performed in SCOPUS and PubMed, limited to English language publications between January 2000 and January 2016. Trials that met the eligibility criteria were scored for risk of bias using the Cochrane Collaborations Risk of Bias Tool. A meta-analysis was performed using Review Manager software version 5.3 (Nordic Cochrane Centre, Cochrane Collaboration).ResultsA total of 7 trials were identified. Meta-analysis demonstrated a modest but statistically significant improvement in HbA1c associated with the use of a telemedicine technology. The mean HbA1c of women using telemedicine was 5.33% (SD 0.70) compared with 5.45% (SD 0.58) in the standard care group, representing a mean difference of −0.12% (95% CI −0.23% to −0.02%). When this comparison was limited to women with gestational diabetes mellitus (GDM) only, the mean HbA1c of women using telemedicine was 5.22% (SD 0.70) compared with 5.37% (SD 0.61) in the standard care group, mean difference −0.14% (95% CI −0.25% to −0.04%). There were no differences in other maternal and neonatal outcomes reported.ConclusionsThere is currently insufficient evidence that telemedicine technology is superior to standard care for women with diabetes in pregnancy; however, there was no evidence of harm. No trials were identified that assessed patient satisfaction or cost of care delivery, and it may be in these areas where these technologies may be found most valuable.     

Ageing is associated with brown adipose tissue remodelling and loss of white fat browning in female C57BL/6 mice

Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age‐induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0.0001). Oral glucose tolerance test showed no disturbance of glucose metabolism. All WAT depots became heavier, and white adipocytes hypertrophied. The subcutaneous and visceral WAT had clusters of beige cells in younger mice, but they were progressively lost by ageing, indicating loss of WAT browning. Older mice had hypertrophied classic brown adipocytes that had larger cytoplasmic lipid droplets than younger mice. Pearson's correlation showed that WAT mass has a weak correlate with BAT mass, although white adipocyte diameter has a strong correlation with classic brown adipocyte size. In conclusion, our results indicate that female C57BL/6 mice have a progressive age‐dependent loss of subcutaneous and visceral WAT browning, and this process runs in parallel with BAT morphological changes towards a fat storer phenotype, independent of cycling or disturbances in glucose metabolism.     

凋亡细胞在db/db自发性糖尿病小鼠颌下腺的分布

目的:观察凋亡细胞在db/db糖尿病小鼠颌下腺中的分布。方法:选取3、4、6、8、10月龄db/db糖尿病小鼠及相应月龄的dh/m~(?)小鼠颌下腺,应用TUNEL标记方法染色后进行图像分析.统计凋亡细胞在颌下腺组织中分布的细胞阳性率。结果:随着糖尿病的发展,颌下腺组织出现腺体萎缩及颗粒曲管数目减少,实质细胞排列不整齐,呈簇状堆集,纤维及血管增多。凋亡细胞在对照组及糖尿病组颌下腺中均有分布,糖尿病组凋亡细胞阳性率高于对照组。糖尿病组与对照组凋亡细胞阳性率随月龄增大均呈增加趋势。结论:db/db糖尿病可导致颌下腺组织萎缩及实质细胞形态学改变;凋亡细胞阳性率在糖尿病组随疾病发展而增加显著。这与糖尿病腺体萎缩和功能受损相一致。     

Alterations of myoepithelial cells in the rat mammary gland during pregnancy, lactation and involution, and after estradiol treatment

Hormone-induced alterations of myoepithelial cells in the mammary gland have not been fully investigated. The aim of the present study was to examine whether myoepithelial cells are altered in response to hormonal conditions. The immunohistochemical findings of smooth muscle actin for myoepithelial cells were studied during pregnancy, lactation and involution, and after estradiol dipropionate (ED) treatment (50, 500, 1000 microg/kg per week for 1-4 weeks) using a total of 71 Wistar female rats. Myoepithelial cells showed a stratified appearance around ducts during pregnancy, extended cytoplasmic processes with wider distance during lactation, and vacuolated cytoplasm after weaning. ED treatment (50-1000 microg/kg per week) for 1 week increased myoepithelial cells to a variable degree, achieving a level similar to that in pregnancy, but ED treatment for 4 weeks reduced them as the dose elevated. The present study showed that the myoepithelial cells became hyperplastic or hypertrophic by low-dose ED treatment within the physiological range, while weaning pups, and excess high-dose ED treatment beyond the physiological range or prolonged ED treatment induced reduction of the myoepithelial cells. Results indicate that myoepithelial cells themselves are also altered by hormonal conditions coordinating the mammary gland development.     

An experimental study on the effects of ethanol and folic acid deficiency, alone or in combination, on pregnant Swiss mice

INTRODUCTION: Ethanol is teratogenic, interferes with folic acid and is extensively used by young women. Our objective was to determine the effects of ethanol and/or folate deficiency on mouse fetuses. METHOD: In Experiment 1, pregnant mice receiving a commercial diet were divided into three groups: control (C), low ethanol dose (LE, 0.4 g/kg), and high ethanol dose (HE, 4.0 g/kg). In Experiment 2, pregnant mice receiving a folate-free diet (FFD) were divided into three groups: folate deficiency (FD), folate deficiency plus a low ethanol dose (FDLE), and folate deficiency plus a high ethanol dose (FDHE). Groups C and FD received saline and the remaining groups received ethanol administered i.p. from the 7th to the 9th gestational day (GD) and were sacrificed on the 18th GD. RESULTS: In Experiment 1, Group HE presented congenital anomalies, late fetal death (LFD), lower fetal length and weight and placental weight and diameter than Groups C and LE. In Experiment 2, there was a smaller number of live fetuses, a larger number of reabsorptions and LFD, a smaller length and lower fetal weight, placental weight and diameter in Groups FDLE and FDHE than in Group FD. CONCLUSION: In animals receiving a commercial diet, a high ethanol dose is deleterious to the pregnancy, inducing congenital anomalies, intrauterine growth restriction, reduction of the placenta and increased LFD, events that did not occur with the low dose. However, with a folate free diet, a low ethanol dose is as deleterious as a high dose.     

去铁敏阻抑ob/ob小鼠海马脑区的Tau蛋白过度磷酸化

目的研究去铁敏(DFO)对ob/ob小鼠脑内Tau过度磷酸化的影响,以探讨铁沉积是否涉及糖尿病(DM)的神经病理。方法繁育12只6月龄ob/ob小鼠,随机分为DFO组和对照组(n=6),分别给予腹腔注射DFO(100 mg·kg^-1)或空白溶剂15d。采用免疫组织化学和Western blot方法,检测小鼠海马脑区的Tau蛋白磷酸化及其调控蛋白激酶和磷酸酶的表达变化;DAB增强的Perl’s染色检测海马铁离子的分布。结果DFO处理后,ob/ob小鼠海马脑区Tau蛋白无明显变化,而在Ser396和Thr231位点的磷酸化水平降低。相应地,DFO组小鼠脑内蛋白激酶GSK3β和CDK5的活性显著下调,磷酸酶PP2A及其活性上调。另外,DFO组小鼠海马脑区的铁染色强度减弱。结论DFO能够有效改善ob/ob小鼠海马脑区的Tau病理,为揭示铁参与DM诱发的神经病理提供了新证据。     

快速老化系小鼠与昆明系小鼠AD相关指标的比较

目的： 观察6月龄的快速老化系SAM-P/8、SAM-R/1小鼠与昆明系小鼠的AD相关指标的变化。方法： 取健康（20±5）g 6月龄SAM-P/8小鼠、SAM-R/1小鼠和昆明系小鼠各14只，雌雄各半，随机分成：SAM-P/8小鼠（AD疾病模型小鼠）、SAM-R/1小鼠对照组和昆明系小鼠对照组，观察上述3组小鼠行为学、神经生化、超微结构、基因表达情况。结果： 6月龄SAM-P/8小鼠1-4d学习成绩、第5 d记忆成绩低于6月龄SMA-R小鼠和昆明系小鼠（P<0.05），真性胆碱酯酶活性则高于6月龄SMA-R/1小鼠和昆明系小鼠（P<0.05）；SAM-P/8小鼠海马神经元超微结构显示明显纤维化，而SAM-R/1小鼠和昆明系小鼠无明显纤维化；SAM-P/8小鼠脑神经细胞的凋亡相关基因表达有明显上调达2倍以上，而SAM-R/1小鼠和昆明系小鼠则未见这些基因有明显上调。SAM-R/1小鼠和昆明系小鼠比较，除基因表达略有差异之外，其它指标无明显差异。结论： 6月龄SAM-P/8小鼠在很多方面已经具备了AD自然发病模型典型特征。而用于正常对照的6月龄SAM-R/1与昆明系小鼠的行为学、TchE活性、超微结构则无显著差异；凋亡相关基因表达差异不明显，而部分基因表达则有一定差异。     

Sleep is increased by weight gain and decreased by weight loss in mice

OBJECTIVE: To determine whether weight loss could reverse excessive sleep in high-fat diet-induced obesity. DESIGN: Three groups of mice participated in the study. A weight gain/loss group was fed with high-fat food for 6 weeks (weight gain), and regular food again for 4 weeks (weight loss). A control group and a weight gain only group were fed with regular food and high-fat food, respectively, for 10 weeks after the baseline. PARTICIPANTS: Adult male C57BL/6 mice. MEASUREMENTS: The amounts of wake, rapid eye movement sleep (REMS) and non-REM sleep (NREMS) were determined at week 0 (baseline), week 6, and week 10. RESULTS: The weight gain/loss group displayed a significant decrease in wakefulness and increases in NREMS and episodes of NREMS during 6 weeks of weight gain, which were reversed during subsequent 4 weeks of weight loss. The weight gain only group displayed significant decrease in wakefulness and increase of NREMS and REMS at both week 6 and week 10. The control group did not show significant sleep alterations during the experiment. CONCLUSION: These observations indicate that sleep alterations induced by weight gain are reversed by weight loss in obese animals. These data may shed light on the mechanisms underlying the well-established association between obesity and sleepiness in humans and may lead to new therapeutic strategies for these 2 increasingly prevalent problems in the modern societies.     

Quantitative image analysis in adipose tissue using an automated image analysis system: differential effects of peroxisome proliferator-activated receptor-alpha and -gamma agonist on white and brown adipose tissue morphology in AKR obese and db/db diabetic mice

Morphometric analysis of adipocytes is widely used to demonstrate the effects of antiobesity drugs or anti-diabetic drugs on adipose tissues. However, adipocyte morphometry has been quantitatively performed by manual object extraction using conventional image analysis systems. The authors have developed an automated quantitative image analysis method for adipose tissues using an innovative object-based quantitative image analysis system (eCognition). Using this system, it has been shown quantitatively that morphological features of adipose tissues of mice treated with peroxisome proliferator-activated receptor (PPAR) agonists differ dramatically depending on the type of PPAR agonist. Marked alteration of morphological characteristics of brown adipose tissue (BAT) treated with GI259578A, a PPAR-alpha agonist, was observed in AKR/J (AKR) obese mice. Furthermore, there was a 22.8% decrease in the mean size of adipocytes in white adipose tissue (WAT) compared with vehicle. In diabetic db/db mice, the PPAR-gamma agonist GW347845X decreased the mean size of adipocytes in WAT by 15.4% compared with vehicle. In contrast to changes in WAT, GW347845X increased the mean size of adipocytes in BAT greatly by 96.1% compared with vehicle. These findings suggest that GI259578A may activate fatty acid oxidation in BAT and that GW347845X may cause adipocyte differentiation in WAT and enhancement of lipid storage in BAT.     

In vivo apoptosis of diabetogenic T cells in NOD mice by IFN-gamma/TNF-alpha

Immunization with mycobacterial preparation such as Bacille Calmette-Guerin (BCG) or complete Freund's adjuvant (CFA) prevents the onset and recurrence of type 1 diabetes in non-obese diabetic (NOD) mice. In this study, we explored the mechanism underlying the down-regulation of diabetogenic T cells by BCG treatment. We found that the potential of splenocytes from BCG-immunized diabetic NOD mice to adoptively transfer diabetes was significantly impaired. BCG immunization sequentially induced the production of TNF-alpha, IFN-gamma and IL-4 by splenocytes, increased the expression of Fas(high) (Apo-1/CD95), Fas ligand (FasL, CD95L) and TNF receptor (TNFR) on T cells leading to T cell apoptosis. The primary role of IFN-gamma and TNF-alpha in BCG-immunotherapy was demonstrated by (i) reversing the immune regulatory effect of BCG by in vivo treatment with neutralizing anti-cytokine antibodies, (ii) inducing effect similar to BCG by treatment with these cytokines. We show that Fas and TNF are two pathways in BCG-induced apoptosis of diabetogenic T cells, since in vitro blocking FasL or TNFR1 with antibody reduced T cell apoptosis and increased T cell proliferative response. In addition, TNF-alpha and agonistic anti-Fas antibody had a synergistic effect on the in vitro apoptosis of diabetogenic T cells. Our results suggest that BCG down-regulates destructive autoimmunity by TNF-alpha/IFN-gamma-induced apoptosis of diabetogenic T cells through both Fas and TNF pathways. These studies provide a novel mechanism for blocking disease recurrence and immune modulating effect of BCG immunization in type 1 diabetes.     

Mutant C57Bl/KsLepr<Superscript>db/+</Superscript> mice as a genetic model of type 2 diabetes mellitus

The genetic model of diabetes mellitus was studied on mutant C57Bl/KsLepr^db/+ mice. These mice were characterized by high concentrations of glucose and glycosylated hemoglobin in the blood, polyuria, polyphagia, polydipsia, progressive obesity, biphasic morphological changes in insular islets of the pancreas (hyperplasia and atrophy), fatty degeneration of the liver, and hypoplasia of the spleen tissue and lymph nodes. Our results indicate that C57Bl/KsLepr^db/+ mice serve as an adequate model of type 2 diabetes mellitus. This model is suitable for testing of therapeutic methods for type 2 diabetes mellitus. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 12, pp. 664–667, December, 2007     

Pregnancy protects against antiangiogenic and fibrogenic effects of angiotensin II in rat hearts

Aim: To investigate the difference between physiological and pathological cardiac remodelling induced, respectively, by pregnancy and angiotensin (Ang) II, and to test the hypothesis that pregnancy protects against Ang II effects. Methods: Female Wistar rats, pregnant (n = 12) and non‐pregnant (n = 12), were implanted with mini‐pumps containing saline (sham) or 150 ng kg^?1 min^?1 Ang II. Ten days later echocardiography and blood pressure measurement were performed. Expression of 22 genes was assessed using RT‐PCR. Microscopic sections of LV were prepared to determine collagen content (Sirius Red staining), vessel density (β‐actin immunolabelling) and myocytes diameter (Toluidine Blue). Results: Heart weight (HW) was increased in Ang II treated groups compared with their controls. Furthermore, HW of Ang II treated pregnant rats (1.0 ± 0.03 g) was higher than that in non‐pregnant sham (0.7 ± 0.02 g), pregnant (0.8 ± 0.01 g) and Ang II treated non‐pregnant (0.8 ± 0.02 g) rats. Relative LV wall thickness showed similar pattern. Aortic pressure was significantly increased in Ang II groups. Collagen content was increased in Ang II (4.0 ± 0.5%) compared with sham (1.5 ± 0.1%) but reduced again when treated rats were pregnant (2.8 ± 0.4%). Vessel density was reduced by 47.8% after Ang II treatment in non‐pregnant and by only 13.9% in pregnant rats. Gene expression analysis showed increased expression of atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), anykrin repeat domain‐containing protein 1 (Ankrd‐1), protein kinase C‐α and ‐δ and tumour suppressor gene TP53 (p53) in Ang II treated groups and upregulation of ANF, BNP and Ankrd‐1 remained when pregnancy was combined with Ang II. Pregnancy reduced expression of: α‐myosin heavy chain, tumour necrosis factor‐α, p53, endothelial nitric oxide synthase and inducible nitric oxide synthase. Conclusion: Pregnancy seems to counteract the detrimental effects of Ang II on fibrosis and angiogenesis in heart. In addition, pregnancy and Ang II lead to partly opposite changes in the expression of some genes important for heart function.     

Histopathological and immunohistochemical evaluation of nitrogen mustard-induced cutaneous effects in SKH-1 hairless and C57BL/6 mice

Sulfur mustard (SM) is a vesicant warfare agent which causes severe skin injuries. Currently, we lack effective antidotes against SM-induced skin injuries, in part due to lack of appropriate animal model(s) that can be used for efficacy studies in laboratory settings to identify effective therapies. Therefore, to develop a relevant mouse skin injury model, we examined the effects of nitrogen mustard (NM), a primary vesicant and a bifunctional alkylating agent that induces toxic effects comparable to SM. Specifically, we conducted histopathological and immunohistochemical evaluation of several applicable cutaneous pathological lesions following skin NM (3.2 mg) exposure for 12–120 h in SKH-1 and C57BL/6 mice. NM caused a significant increase in epidermal thickness, incidence of microvesication, cell proliferation, apoptotic cell death, inflammatory cells (neutrophils, macrophages and mast cells) and myleoperoxidase activity in the skin of both mouse strains. However, there was a more prominent NM-induced increase in epidermal thickness, and macrophages and mast cell infiltration, in SKH-1 mice relative to what was seen in C57BL/6 mice. NM also caused collagen degradation and edema at early time points (12–24 h); however, at later time points (72 and 120 h), dense collagen staining was observed, indicating either water loss or start of integument repair in both the mouse strains. This study provides quantitative measurement of NM-induced histopathological and immunohistochemical cutaneous lesions in both hairless and haired mouse strains that could serve as useful tools for screening and identification of effective therapies for treatment of skin injuries due to NM and SM.     

Effects of captopril on arterial blood pressure,plasma renin activity and vasopressin concentration in sodium-repleted and sodium-deficient goats: A serial study during pregnancy,lactation and anestrus

The effects of captopril (intravenous loading dose of 20 mg, 1 h later followed by 10 mg infused during the next h) on arterial blood pressure and plasma renin activity were followed in 4 goats during the last months of pregnancy, during lactation and during anestrus. Experiments were made both when the animals were sodium-repleted and sodium-deficient. Furosemide and dietary restriction were used to deprive the animals of sodium. In sodium-replete animals, captopril caused a more pronounced fall in mean arterial blood pressure and a larger increase in plasma renin activity (PRA) when the animals were pregnant than when they were lactating or in anestrus. During sodiumdeficient conditions the response was similar as during sodium repletion in pregnant goats. In anestral goats, PRA rose in response to captopril, but the blood pressure fall was similar as when the goats were sodium-replete. In lactating sodium-deficient goats, captopril caused a marked fall in mean arterial blood pressure concomitant with a 2–3 times higher rise in PRA than during corresponding sodium-repletion experiments. The respiratory rate was elevated in pregnant animals and increased further during captopril. The plasma vasopressin concentration did not change during captopril-induced hypotension. If the blood pressure fell ≥10 mmHg the animals became very quiet and occasionally they fell asleep. All goats delivered healthy kids. The fact that the blood pressure fall was marked and consistent in all animals during pregnancy, but less and more variable during anestrus indicates that the activity of the renin-angiotensin system is of greater importance for blood pressure maintenance during pregnancy than during anestrus. The exaggerated effects in lactating sodium-deficient animals were probably due to a more efficient salt depletion, these animals losing extra salt via the milk.