Association between the Use of Diuretics and Size Reduction in Pediatric Atrial Septal Defect

Background and Objectives@#While diuretics are sometimes used in atrial septal defect (ASD) treatment, their effect on ASD size reduction remains unclear. We aimed to evaluate the efficacy of diuretics in ASD size reduction in pediatric patients. @*Methods@#We retrospectively reviewed the medical records of patients with secundum ASD (size ≥10 mm), between 2005 and 2019. Patients were divided into two groups based on the diuretic administration. @*Results@#Of the 73 enrolled patients, 40 received diuretics. The initial age at ASD diagnosis (2.8±1.7 vs. 2.5±2.0 years, p=0.526) and follow-up duration (22.3±11.4 vs. 18.7±13.2 months, p=0.224) were not significantly different between the groups. The ASD diameter at the initial diagnosis (13.7±2.0 vs. 13.5±3.4 mm, p=0.761) and the indexed ASD diameter (25.5±5.9 vs. 26.9±10.3 mm/m2 , p=0.493) were also not significantly different between two groups. The ASD diameter significantly increased in the non-diuretic group during follow-up (0.0±2.9 vs. +2.6±2.0 mm, p<0.001). The indexed ASD diameter significantly decreased in the diuretic group during follow-up (−5.7±6.5 vs. +0.2±3.9 mm/m 2 , p<0.001). In the linear mixed model analysis, diuretic use was associated with ASD diameter decrease (p<0.001) and indexed ASD diameter reduction (p<0.001) over time. Device closure was more frequently performed in the diuretic (75.0%) than in the non-diuretic group (39.4%). @*Conclusions@#Patients receiving diuretics are less likely to undergo surgery. The diuretics administration may be associated with the use of smaller ASD devices for transcatheter treatment through ASD size reduction.

Medical Expenses of the Family Members of Brain Dead Organ Donors and National Assistance / 대한이식학회지

BACKGROUND: Analyzing the medical expenses of the family members of brain dead organ donors would be helpful in ascertaining better ways of applying national assistance, which is important for promotion of brain dead organ donation. METHODS: We collected data regarding the medical expenses of 119 brain dead organ donors from January 2009 to December 2013 at a single institution that specializes in organ donation. Donation year, cause of brain death, age, and admission days were deemed factors affecting medical expenses, and these were analyzed. Medical expenses were compared with national assistance (maximum of 1.8 million Korean won [KRW]). RESULTS: Average age of donors was 42.7 years, and, in the older age group, there was a lower average for medical expenses (P=0.025). Brain dead organ donations that were consented to within 2 days after the brain death comprised 41.2%, and medical expenses increased as the consent days were delayed (P<0.001). Average medical expense for donor families was 2,161,297 KRW, and the average national assistance to the families was 577,056 KRW. The medical expenses of 73 donors (61.3%) were below the national assistance maximum; 19 (16.0%) had no charges of their own with other insurance coverage. CONCLUSIONS: National assistance for medical expenses to family members of brain dead organ donors is necessary in Korea, where the rate of brain dead organ donation is very low. As 61% of donors were covered below the maximum assistance amount, there could be additional ways to utilize the remaining budget.

Attitude Favorability towards Organ Donation in Family Members of Brain Dead Organ Donors / 대한이식학회지

BACKGROUND: Analyzing the attitudes toward organ donation and the factors that influence such attitudes is fundamental to improving the quality of management for the process of brain dead organ donation. METHODS: We interviewed 23 primary carers of donors after a minimum period of one year post organ donation from a single hospital, from 2008 to 2011. This telephone survey analyzed factors including relationship with the donor and the impact of such factors on making the decision for donation and attitude towards organ donation. RESULTS: With respect to the carers' relationship with the donor, seven carers who participated in the interview were spouses (30.4%), six were parents (26.0%), three were offspring (13.0%), and seven were siblings (30.4%). Ten of the decision makers (43.4%) were not legal priority holders. Twenty-two interviewees (95.6%) experienced no regret for their decision to go through with the donation. Fifteen participants (65.1%) were willing to donate their own organs in case of brain death, and the favorability towards organ donation was significantly related to the satisfaction with their experience of medical services during the process of organ donation. CONCLUSIONS: Organ donation after brain death is still viewed favorably by carers even after the bereavement period. Positive attitude and favorability toward organ donation were significantly related to the satisfaction with the medical service. We suggest interventions to improve the quality of medical services in order to promote organ donation.

Application of SYBR Green real-time PCR assay for the specific detection of Salmonella spp / 대한수의학회지

The aim of this study was to applicate and evaluate a SYBR Green real-time PCR for the specific detection of Salmonella spp. Specificity of the PCR method was confirmed with 48 Salmonella spp. and 5 non-Salmonella strains using invA gene primer. The average threshold cycle (C(T)) of Salmonella spp. was 11.83 +/- 0.78 while non-Salmonella spp. was 30.86 +/- 1.19. Correlation coefficients of standard curves constructed using C(T) versus copy number of Salmonella Enteritidis ATCC 13076 showed good linearity (R2 = 0.993; slope = 3.563). Minimum level of detection with the method was > 10(2) colony forming units (CFU)/mL. These results suggested that the SYBR Green real-time PCR might be applicable for the specific detection of Salmonella spp. isolates.

Development of a novel enzyme-linked immunosorbent assay to detect anti-IgG against swine hepatitis E virus

Swine hepatitis E virus (HEV) is widespread throughout pigs in both developing and industrialized countries. This virus is an important zoonotic agent and a public concern worldwide. Infected pigs are asymptomatic, so diagnosing swine HEV relies on detection of the virus or antibodies against the virus. However, several obstacles need to be overcome for effective and practical serological diagnosis. In this study, we developed an enzyme-linked immunosorbent assay (ELISA) that used a purified recombinant capsid protein of swine HEV. The potential clinical use of this assay was evaluated by comparing it with a commercial kit (Genelabs Technologies, Diagnostics, Singapore). Results of the ELISA were highly correlated with those of the commercial kit with a sensitivity of 97% and specificity of 95%. ROC (receiving operator characteristic) analysis of the ELISA data produced a value of 0.987 (95% CI, 0.977~0.998, p < 0.01). The cut-off value for the ELISA was also determined using negative pig sera. In summary, the HEV-specific ELISA developed in the present study appears to be both practical and economical.

The effects of Germanium biotite on the adsorptive and inhibition of growth abilities against E. coli and Salmonella spp. in vitro / 대한수의학회지

Germanium biotite, a natural mineral, has been used as a feed supplement to reinforce innate immune ability. The aim of the present study was to evaluate the effects of germanium biotite on the adsorptive and inhibition of growth abilities against Escherichia (E.) coli and Salmonella spp. in vitro. Two strains of enterotoxigenic E. coli and four strains of two Salmonella serotypes (Salmonella Derby and Salmonella Typhimurium), major bacterial diarrheal pathogens, were used for this experiment. The absorptive ability of germanium biotite against most Salmonella used in present experiment was observed weakly. The germanium biotite, however, showed significant effect of bacterial growth inhibition in most experiment bacteria. These results suggest that the use of the germanium biotite as feed supplement could alleviate diarrhea following inhibition of bacteria growth. It is also presumed that antibiotics usage for farm animals, considered as causes of antibiotic residue in meat and emerging antibiotic resistance, could be reduced through the use of germanium biotite as a feed supplement, in place of antibiotics used for the prevention of diarrhea.

Generation of transgenic corn-derived Actinobacillus pleuropneumoniae ApxIIA fused with the cholera toxin B subunit as a vaccine candidate

Corn, one of the most important forage crops worldwide, has proven to be a useful expression vehicle due to the availability of established transformation procedures for this well-studied plant. The exotoxin Apx, a major virulence factor, is recognized as a common antigen of Actinobacillus (A.) pleuropneumoniae, the causative agent of porcine pleuropneumonia. In this study, a cholera toxin B (CTB)-ApxIIA#5 fusion protein and full-size ApxIIA expressed in corn seed, as a subunit vaccine candidate, were observed to induce Apx-specific immune responses in mice. These results suggest that transgenic corn-derived ApxIIA and CTB-ApxIIA#5 proteins are potential vaccine candidates against A. pleuropneumoniae infection.

Catechins inhibit angiotensin II-induced vascular smooth muscle cell proliferation via mitogen-activated protein kinase pathway

Catechins, components of green tea, reduce the incidence of cardiovascular diseases such as atherosclerosis. Angiotensin II (Ang II) is highly implicated in the proliferation of vascular smooth muscle cells (VSMC), resulting in atherosclerosis. The acting mechanisms of the catechins remain to be defined in the proliferation of VSMC induced by Ang II. Here we report that catechin, epicatechin (EC), epicatechingallate (ECG) or epigallocatechingallate (EGCG) significantly inhibits the Ang II-induced [3H]thymidine incorporation into the primary cultured rat aortic VSMC. Ang II increases the phosphorylation of the extracellular signal-regulated protein kinase 1/2 (ERK 1/2), c-jun-N-terminal kinase 1/2 (JNK 1/2), or p38 mitogen-activated protein kinases (MAPKs) and mRNA expression of c-jun and c-fos. The EGCG pretreatment inhibits the Ang II-induced phosphorylation of ERK 1/2, JNK 1/2, or p38 MAPK, and the expression of c-jun or c-fos mRNA. U0126, a MEK inhibitor, SP600125, a JNK inhibitor, or SB203580, a p38 inhibitor, attenuates the Ang II-induced [3H]thymidine incorporation into the VSMC. In conclusion, catechins inhibit the Ang II-stimulated VSMC proliferation via the inhibition of the Ang II-stimulated activation of MAPK and activator protein-1 signaling pathways. The antiproliferative effect of catechins may be associated with the reduced risk of cardiovascular diseases by the intake of green tea. Catechins may be useful in the development of prevention and therapeutics of vascular diseases.

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Resveratrol has been shown to possess antioxidant and anticancer activities, but little is known on the effect of resveratrol derivatives. Recently we have isolated resveratrol and its dimers and trimers from peony (Paeonia lactiflora) seeds, and reported their strong antioxidant and cytotoxic activity. In the present study, we have evaluated cellular effects of resveratrol derivatives; viniferin, gnetin H, and suffruticosol B on the proliferation and apoptosis in HL-60 cells in vitro. All resveratrol and its derivatives reduced viability of HL-60 cells in a dose-dependent manner with their IC(50)values of 20-90 micrometer. Ascending orders of IC(50)values were suffruticosol B, gnetin H, viniferin and resveratrol respectively. HL-60 cells treated with the four stilbenes exhibited the distinct morphological changes characteristics of cell apoptosis such as chromatin condensation, apoptotic bodies, and DNA fragmentations. A time-dependent histogram of the cellular DNA analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 micrometer resveratrol for 0-24 h. Cells treated with 25 micrometer of resveratrol, viniferin, gnetin H, and suffruticosol B for 24 h resulted in increment of sub-G1 population by 51, 5, 11 and 59%, respectively. Treatment of cells with 0-20 micrometer resveratrol for 5 h produced a concentration-dependent decrease in cytochrome P450 (CYP) 1B1 mRNA levels. Suffruticosol B also suppressed CYP1B1 gene expression. These results demonstrated that resveratrol oligomers also strongly suppressed HL-60 cell proliferation, and induced DNA damage. In addition, CYP1B1 gene supression may suggest an involvement in the resveratrol-induced apoptosis in HL-60 cells.

Estrogen and Enalapril attenuate the Development of Right Ventricular Hypertrophy induced by Monocrotaline in Ovariectomized Rats

The present study evaluated the importance of ovarian functions and the renin-angiotensin system in the progression of the right ventricular (RV) hypertrophy. Female Sprague-Dawley rats were bilaterally ovariectomized (Ovx) and injected with monocrotaline (MCT, 60 mg/kg, sc). Four weeks after MCT-treatment, only the male and Ovx female rats showed marked RV hypertrophy. The hypertrophied RV of the male-MCT and Ovx-MCT rats exhibited remarkably elevated renin mRNA levels. Gene expression levels of angiotensinogen, TGF-beta1, and endothelin-1 in the hypertrophied RV also increased, but to the less degree than did the renin mRNA. To investigate beneficial effects of estrogen or enalapril on progression of the pulmonary hypertension and RV hypertrophy, histological changes of the lung and heart were examined. Sham-MCT female rats showed histological changes indicating pulmonary hypertension without RV hypertrophy. In contrast, Ovx-MCT rats showed marked RV hypertrophy with pathological changes, denoting severe pulmonary and myocardial injuries. Estrogen-or enalapril-treated Ovx-MCT rats did not show RV hypertrophy, and showed remarkably ameliorated ultrastructural changes in the lung and RV. These results from this rat model suggest that both estrogen and inhibition of the renin-angiotensin system have protective functions against the development of the pulmonary hypertension and cardiac remodeling.

Colocalization of ANG II and mRNA for the Renin-Angiotensin System Components in Cultured Rat Glomerular Epithelial and Mesangial Cells / 대한해부학회지

Mesangial cells are found to have renin and angiotensin II-AT1 receptors, but the presence of other components of the renin-angiotensin system and production of angiotensin II within the cell have not been demonstrated. The presence of the renin-angiotensin system components in the glomerular epithelial cell has not been previously reported. We studied expression of each component of the renin-angiotensin system in primary cultured rat glomerular epithelial cells and mesangial cells. We assessed mRNA expression by RT-PCR and the presence of angiotensin II by immunocytochemistry. Both cultured glomerular epithelial cells and mesangian cells expressed mRNA for components of the renin-angiotensin system such as renin, angiotensinogen and angiotensin II type 1A and 1B receptor subtypes. Immunocytochemical studies with specific antibody for angiotensin II demonstrated significant immunoreactivity in both glomerular epithelial cells and mesangian cells. These results, for the first time, provide direct evidence that both the glomerular epithelial cells and mesangian cells contain a complete renin-angiotensin system and generate angiotensin II with intracellular mechanisms. Further studies are required to define the subcellular localization of angiotensin II with electron microscopy and to elucidate the physiological importance of the intracellular reninangiotensin system.

Enhanced Expression of Aldosterone Synthase and Adrenomedullin in Left and Right Ventricular Hypertrophy in Rats

The pathophysiological implications of aldosterone and adrenomedullin in the cardiac ventricular hypertrophy were examined. Male Sprague-Dawley rats were treated with deoxycorticosterone acetate (DOCA)-salt and monocrotaline (MCT) to selectively elicit left and right ventricular (LV, RV) hypertrophy, respectively. The mRNA expression of aldosterone synthase and adrenomedullin in LV and RV was determined by reverse transcription-polymerase chain reaction. The expression of aldosterone synthase and adrenomedullin was increased in LV, while not altered significantly in RV of DOCA-salt-treated rats. On the contrary, the expression was not significantly altered in LV, but increased in RV of MCT-treated rats. The enhanced expression of aldosterone synthase may be causally related with the development of ventricular hypertrophy, and the increased expression of adrenomedullin may act as a counter-regulatory mechanism.

Phytoestrogen-Induced Phosphorylation of MAP Kinase in Osteoblasts is Mediated by Membrane Estrogen Receptor

We have previously demonstrated that phytoestrogens isolated from safflower seeds significantly attenuated bone loss in ovariectomized rats, and directly stimulated proliferation and differentiation of cultured osteoblastic cells. In an attempt to elucidate underlying cellular mechanisms, in the present study we investigated effects of 17beta-estradiol (E2) and phytoestrogens such as matairesinol and acacetin, a type of lignan and flavonoid, respectively, on activation of mitogen activated protein (MAP) kinases, extracellular signal-regulated kinase 1 (ERK1) and ERK2, in cultured osteoblastic ROS 17/2.8 cells. Western blot analysis with anti-MAP kinase antibody showed that a wide range concentrations (10(-14) to 10(-6) M) of E2 as well as both phytoestrogens induced rapid and transient activation of ERK1/2 through phosphorylation within minutes. Maximum activation of MAP kinases by E2 and phytoestrogens were observed at 10 and 15 min, respectively. E2-induced phosphorylation of ERK1/2 returned to the control level at 30 min, whereas phytoestrogen-induced phosphorylation was maintained at high level until 30 min. PD-98059, a highly selective inhibitor of MAP kinase, prevented phosphorylation of ERK1/2 in the cells treated either with E2 or phytoestrogens. To examine a possible involvement of estrogen receptor in the activation process of MAP kinase, Western blot analysis was performed in the presence and absence of the estrogen receptor antagonists, ICI 182,780 and tamoxifen. These antagonists blocked MAP kinase phosphorylation induced not only by E2, but also by the phytoestrogens. To the best our knowledge, this study is the first to demonstrate that phytoestrogens such as flavonoid and lignan extracted from safflower seeds produce a rapid activation of MAP kinase, at least partially via membrane estrogen receptor of the cultured osteoblastic cells.

Increased expression of nitric oxide synthases in left and right ventricular hypertrophy

The present study was aimed to explore pathophysiological implications of nitric oxide in the development of left and right ventricular hypertrophy. To induce selective left and right ventricular hypertrophy, rats were made two-kidney, one clip (2K1C) hypertensive and treated with monocrotaline (MCT), respectively. Six weeks later, the hearts were taken and their ventricular tissue mRNA and protein expression of endothelial constitutive isoform of nitric oxide synthase (NOS) were determined by reverse transcription-polymerase chain reaction and Western blot analysis, respectively. In 2K1C hypertensive rats, the expression of NOS mRNA was increased in parallel with its proteins in the left ventricle, but not in the right ventricle. In MCT-treated rats, the expression of NOS mRNA and proteins were proportionally increased in the right ventricle, but not in the left ventricle. These results suggest that the expression of NOS is specifically increased in association with the ventricular hypertrophy, which may be a mechanism counteracting the hypertrophy.

Expression of Brain-Derived Neurotrophic Factor and its mRNA in Catecholaminergic Neurons of the Rat Lower Brainstem after Colohicine Treatment or Hemorrhage / 대한해부학회지

Widespread brain-derived neurotrophic factor (BDNF) mRNA expression has been detected in the region of catecholamine groups of the rat lower brainstem, while few BDNF-immunoreactive cells were found in this area. In the present study, a double-color immunofluorescence (IF) technique for BDNF and tyrosine hydroxylase (TH) after colchicine treatment was employed to evaluate the possible presence of BDNF immunoreactivity in the catecholamin-ergic cells of rat lower brainstem. Additionally, a double-color IF technique for BNDF and TH and in situ hybridiza-tion for BDNF mRNA were performed to see effects of hemorrhage on the expression of BDNF and its mRNA. We detected many new BDNF-immunoreactive cells in the A1, A2, A4, A6-A10 and C1-C3 cell groups and in the other lower brainstem nuclei where, without colchicine treatment, BDNF mRNA was expressed, but not BDNF immunoreactivity. In addition, the catecholaminergic neurons were found to express BDNF immunoreactivity with the co-existence being greatest, in percentage terms, in medullary catecholaminergic cell groups. Hypotensive hemorrhage, which activates medullary catecholaminergic neurons, induced the expression of BDNF immunoreactivity in catecholaminergic neurons (A1/C1 and C2) and increased the number of BDNF mRNA-containing neurons in the area. These results demonstrate that BDNF is regulated by activity in medullary catecholaminergic cell groups involved in central cardiovascular regulation.

Effect of brain angiotensin II receptor antagonists and antisense oligonucleotide on drinking and renal renin in rats

The physiological roles of brain angiotensin II in mediating water deprivation-induced drinking and in regulating renal renin release were assessed in male Sprague-Dawley rats. Specific AT1 receptor antagonists, losartan and SK 1080, and antisense oligonucleotide (AS-ODN) directed to AT1 receptor mRNA were intracerebroventricularly (i.c.v.) administered in conscious unrestrained rats. When water was given 20 min after i.c.v. injection of AT1 receptor antagonists in 48-h water-deprived rats, losartan and SK 1080 produced approximatly 20% and 50% decrease in 1-h water intake, respectively. In contrast, i.c.v. treatment of the AS-ODN to AT1 receptor mRNA for 24-h did not alter 1-h water intake in 24-h water-deprived rats, but prevented the increase in overnight water intake after 24-h water-deprivation. Six-day i.c.v. treatment of AS-ODN did not alter either the basal plasma renin concentration or renal cortical levels of renin and renin mRNA. The present results suggest that endogenous brain Ang II plays an important role in thirst and water intake through AT1 receptors, but further studies are required to elucidate its regulatory role in renal renin synthesis.

Spectral analysis of heart rate variability during passive standing after ethanol ingestion

The purpose of the present study was to evaluate cardiovascular regulation during passive standing (PS) after ethanol ingestion by spectral analysis of heart rate variability (HRV) in flushed and nonflushed subjects. Of 24 young male subjects, 8 belonged to flushed group (F) and 16 to nonflushed group (NF). Two sessions of 10-min PS were performed before and after ethanol (0.5 g/kg) ingestion. Powers of R-R interval variability in very low frequency (VLF, 0~0.05 Hz), low frequency (LF, 0.05~0.15 Hz) and high frequency (HF, 0.15~0.50 Hz) bands, normalized powers (LFn and HFn) and LF/HF ratio were obtained. After ethanol ingestion, F showed higher heart rate than NF. PS increased LFn (+ 22.9+/-3.6 in NF, + 12.8+/-4.7 in F, in normalized units) and LF/HF (+ 3.10+/-0.57 in NF, + 3.00+/-1.08 in F) and decreased HFn powers. Ethanol ingestion increased LFn and LF/HF and decreased HFn. PS after ethanol resulted in higher LFn and LF/HF and lower HFn than the prior PS. F showed a greater and more sustained HRV change than NF after ethanol. In conclusion, PS or ethanol ingestion increased LFn and LF/HF and decreased HFn. Flushed subjects showed an accentuated HRV response to ethanol.

The propensity to depression and anxiety in children

BACKGROUND: The goals of this study are to investigate the propensity to depression and anxiety in children, and also, to investigate its relationship to the family structure, their life events, and school achievement. We have attempted to aid the continuous and comprehensive management of children with depression and anxiety in a field of family practice. METHODS: A group of 797 boys and girls in 5th and 6th were selected grades a elementary school in their, In the area of ll-san and In-cheon city in August, 1997. Making use of the Kovacs' Children's Depression Inventory(CDI, 1977) and the Spielberger's State-Trait Anxiety Inventory for Children(STAIC, 1973), we investigated the propensity to depression and anxiety by self-rating. At the same time, the general characteristics(gender, age, resideuce, family structure), life events(death single parent, divorced family, death of a sibling, family discord between husband), and school achievement were investigated and assessed their relationship. RESULTS: The Children's Depression Inventory score was 11.69, the State Anxiety Inventory score was 31.51, and the Trait Anxiety Inventory score was 31.49. The CDI score were significantly higher in females, sixth year students, residents execpt for those living in an apartment or villa, and low school achievement group(P<0.01, P<0.05), There was no significance between CDI score and age, whether or not a dual-income family, death of a sib, hospitalization within 6 months, and family discord between husband and wife. The STAIC score was significantly higher for old age, female, sixth year students, and low school achieve menu group(P<0.01), and there was no significance between the STAIC score and residence, whether or not a dual-income family, death of a sibling, hospitalization within 6 months, and family discord between husband and wife. CONCLUSIONS: According to our results, there was a significant correlation between gender, school years, school achievement and a propensity to depression and anxiety. Therefore, family physician should be more involved in family intervention and anticipatory guidance upon medical examination and treatment, if he or she has a symptoms of anxiety and depression.

Effects of angiotensin converting enzyme inhibition on gene expression of the renin-angiotensin system in rats

To investigate interaction of angiotensin converting enzyme (ACE) inhibitor with local tissue renin-angiotensin system (RAS), changes in gene expression of the RAS components in various tissues in response to chronic administration of an ACE inhibitor, enalapril, were examined in Sprague-Dawley male rats. Enalapril was administered in their drinking water (3 ~ 4 mg/day) over 8 wk. Plasma and renal ACE activity increased significantly after 4 and 8 wk of enalapril treatment. Renin levels of the plasma and kidney of the enalapril-treated rats markedly increased after 4 wk and decreased thereafter, but still remained significantly higher than those of control rats. Kidney mRNA levels of renin markedly increased after 4 and 8 wk of enalapril treatment, but those of angiotensinogen and ANG II-receptor subtypes, AT1A and AT1B, did not change significantly. The liver expressed genes for renin, angiotensinogen and AT1A receptor subtype, but AT1B receptor subtype mRNA was not detectable by RT-PCR. None of mRNA for these RAS components in the liver changed significantly by enalapril treatment. The hypothalamus showed mRNA expressions of renin, angiotensinogen, AT1A and AT1B receptor subtypes. AT1A receptor subtype mRNA was more abundant than AT1B receptor subtype in the hypothalamus as shown in the kidney. However, gene expression of the RAS components remained unchanged during 8-wk treatment of enalapril. In the present study, chronic ACE inhibition increased plasma and renal levels of ACE and renin, but did not affect mRNA levels of other RAS components such as angiotensinogen, ANG II receptor subtypes in the kidney. Gene levels of the RAS components in the liver and hypothalamus were not altered by chronic treatment of enalapril. These results suggest the differential expression of the RAS components in response to enalapril, and localized action and some degree of tissue specificity of enalapril.

Cardiovascular Effects of Endogenous GABA in the Nucleus Tractus Solitarius

BACKGROUND: The nucleus tractus solitarius (NTS), the region of the brain stem in which primary baroreceptor afferents teminate, is critically important in the normal regulation of arterial pressure (AP). In the NTS, excitatory amino acids such as L-glutamate serve as the main neurotransmitter in the regulation of AP. However, the function of GABA in the NTS has not been established. To test the function of GABA, we applied GABAergic agents to the NTS. METHODS: The experiments were conducted on adult male Sprague-Dawley rats weighing 300-500g. A cannula (PE-50 tubing filled with heparinized saline) was inserted into the femoral artery for recording of AP and heart rate(HR). Another cannula was inserted into the femoral vein for administration of nitroprusside or phenylephrine. After rats were placed on a sterotaxic instrument, the dorsal surface of the medulla was exposed, and with the aid of a surgical microscope, the NTS was visualized. Drug injections were made into the NTS using single- or three-barreled grass micropipettes pulled to an outer diameter of 80-100(micro)m and connected to a 1(micro)l Hamilton syringe. RESULTS: The follwing results were obtained in this experiment. Injection into the NTS of 10 or 20 nmol nipecitic acid, a selective inhibitor of GABA untake, produced an increase in AP. The pressor responses evoked by two doses of nipecotic acid were not significantly different. Injection of GABA(A) agonist, musciml(5 pmol in 80 nl artificial CSF) and GABA(B) agonist, baclofen (20 pmol in 80 nl) into the NTS of urethane-anesthetized rats prodused an increase in AP of 16.6+/-1.3 and 27.6+/-1.5 mmHg, respectively. Thus the pressor response to GABA(B) agonist was greater than to GABA(A) agonist. On the other hand, microinjection of GABA(A) antagonist, bicuculline and GABA(B) antagonist, phaclofen into the NTS decreased AP by approximately 13.4+/-1.0 and 20.9+/- mmHg, respectively. Thus injection of nipecotic acid into the NTS was greater in control group compared with the muscimiol or baclofen groups. The AP changes caused by i.v. injection of nitroprusside or phenylephrine were smallest in control group and greatest in the baclofen group. When calculated as baroreflex sensitivity, the change was greatest in control group and smallest in the baclofen group. CONCLUSION: From these results it was concluded that GABA in the NTS plays an important role in the regulation of AP, especially through GABA(B) receptors, and have an inhibitory effect on baroreceptor reflex.