bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-BPR03-7: ANTIHYPERTENSIVE EFFECT OF ANGIONTENSIN RECEPTOR-NEPRILYSIN INHIBITION IN PERITONEAL DIALYSIS PATIENTS
Authors: Ishikawa Risa , Ishiyama Katsuya , Yabana Ikuko , Hirose Takuo , Sato Toshiyuki , Matsumoto Keiji , Kato Toshiko , Kamada Ayaka , Ito Hiroki , Nakayama Shingo , Hashimoto Hideaki , Nakamura Hanna , Kimura Tomoyoshi , Mori Takefumi 
Published: January 2023

Objectives:
Blood pressure and volume control is required in patients undergoning peritoneal dialysis (PD). Residual renal function play an important role in PD vintage and mortality, and also dependent on blood pressure and volume control. Sacubitril-valsartan, and angiotensin receptor-neprilysin inhibitor (ARNI), has been approved to use for blood pressure control in Japan. However, the antihypertensive effect of sacubitril-valsartan in PD patients is not well known. Thus, the present study was designed to determine the efficacy and safety of ARNI in hypertensive patients undergoing PD.

Methods:
Hypertensive end-stage kindey disease (ESKD) patients and systolic blood pressure of more than 135 mmHg despite of other hypertensive drugs was administered sacubitril-valsartan. Clinical parameters such as home blood pressure, body weight, brain natriuretic peptide and urine volume was monitored. Body fluid composition was analyzed by bioimpedance method.

Results:
Eleven PD patients received sacubitril-valsaltan at a dose between 100–400 mg. Blood pressure decreased in seven patients. Then, those who responded (Res group, n = 7) to sacubitril-valsartan was compared to those did not responded (Non-Res group, n = 4). Significantl decrease in blood pressure was observed in Res group by 16.9 ± 10.2mmHg, while increase was observed in Non-Res group by 10.8 ± 7.8mmHg. Plasma BNP tended to decrease in both groups but did not reach to a level of significance. Body weight, urine volume, extracelullar water / total body water did not change in either group.

Conclusions:
Antihypertensive effect of sacubitril-valsartan was observed in limited patients of ESKD patients undergoing PD. However, BNP was reduced in most patients treated with sacubitril-valsartan with no adversed effects. Although ARNI could be beneficial antihypertensive drugs for cirtain hypertensive ESKD patients undergoing PD, further study is requied.
PS-BPR03-9: A CASE OF RENAL JUXTAGLOMERULAR CELL TUMOR THAT WAS PREOPERATIVELY DIAGNOSED BY SELECTIVE RENAL VENOUS SAMPLING
Authors: Okamoto Kentaro , Taura Daisuke , Yokogawa Kasumi , Ohno Tsuyoshi , Shimizu Hironori , Fujita Haruka , Sugawa Taku , Hakata Takuro , Ueda Yohei , Yamauchi Ichiro , Fujii Toshihito , Inagaki Nobuya 
Published: January 2023

A 26-year-old woman without a family history of hypertension was referred to our hospital for a further examination of juvenile hypertension. At 25 years of age, she had headaches, and hypertension (210/120 mmHg) was first noted. A diagnostic examination to assess the hypertension was performed and she was hypokalemic with serum K 2.9 mEq/L. Moreover, the plasma renin activity (PRA) and plasma renin concentration (PRC) was markedly elevated (18.7 ng/mL/h and 196.3 pg/mL), and plasma aldosterone concentration (PAC) was also elevated (291 pg/mL). A captopril challenge test showed a mildly increased PRA response (15.5 ng/mL/h to 20.3 ng/mL/h), but MR angiography and renogram showed no findings suggestive of renal vascular hypertension. On the other hand, dynamic contrast-enhanced CT showed a small neoplastic lesion (10 mm in diameter) without enhancement in the early phase, but with slight enhancement in the late phase, on the left renal upper pole. We performed renal vein sampling, but no obvious lateralization in PRA was found at the main trunk level of the left and right renal veins (14.0 vs. 14.3 ng/mL/h). Therefore, we performed more selective sampling of the branches of the left renal vein and found that PRA in the upper pole branch of the left renal vein was approximately 3.7 times higher than in the inferior pole branch, the main trunk of the left and right renal veins, and the inferior vena cava (51.5 ng/mL/h vs. 14.0–15.1 ng/mL/h). Based on these results, we made a preoperative diagnosis that the tumor in the upper pole of the left kidney was a juxtaglomerular cell tumor producing renin excessively and decided to perform partial left nephrectomy.
Juxtaglomerular cell tumors (JCT) are very rare diseases that primarily occur in adolescents and young adults. Excessive renin secretion from the tumor causes secondary hypertension, and hypokalemia. It has been reported that renal vein sampling, in addition to CT and MRI scans, is useful for preoperative localization of JCT. However, the usual method of sampling only the main trunk of the renal vein fails to detect lateralization of the PRAs in many cases. In the present case, we were able to identify the localization of the tumor by performing sampling of the branches of the renal vein. We herein report on the usefulness of selective renal vein sampling for the preoperative diagnosis of JCT.
PS-BPR03-11: A CASE OF MALIGNANT PHASE HYPERTENSION ASSOCIATED WITH PRIMARY ALDOSTERONISM
Authors: Murai Sayaka , Koike Tsutomu , Arisawa Yu , Fujioka Hayato , Kakeshita Kota , Yamazaki Hidenori , Kinukawa Koichiro 
Published: January 2023

Background:
Primary aldosteronism is associated with low plasma renin levels, while malignant phase hypertension is generally associated with raised renin activity. Therefore, these two conditions are at opposite ends of the renin spectrum, so in theory their co-existence would be unusual.

Case presentation:
We present a case of a 41-year-old male with uncontrolled hypertension on multiple antihypertensive drugs. He discontinued these drugs for three days, thereafter he admitted to our hospital with congestive heart failure and acute ischemic stroke. He manifested malignant phase hypertension (blood pressure 216/130 mmHg; Keith-Wagener IV) accompanying renal dysfunction (serum creatinine 2.4 mg/dL), high plasma aldosterone concentration (PAC, 221 pg/mL) and mildly elevated plasma renin activity (PRA, 3.0 ng/mL/hr). A computed tomography did not reveal the presence of adrenal mass. After the treatment for congestive heart failure, the reassessment for endocrine causes of hypertension showed high level of PAC (468 pg/mL) and low level of PRA (0.2 ng/mL/hr), resulting in a high PAC/PRA ratio under the treatment with angiotensin-converting enzyme inhibitor. Adrenal venous sampling (AVS) confirmed the excessive aldosterone secretion from bilateral adrenal glands. Given these findings, we diagnosed him with idiopathic aldosteronism. After an addition of the mineralocorticoid receptor antagonist, he could keep his blood pressure under control.

Conclusions:
PRA in patients with primary aldosteronism could be increased under the conditions in which renin release from the kidney is overstimulated by glomerular ischemia, leading to an incorrect diagnosis of primary aldosteronism. Repeated endocrine assessment including the measurement of PRA and PAC should be considered to reveal the cause of malignant phase hypertension.
PS-B03-6: COMPARISON OF SUPPRESSIVE EFFECTS ON CATECHOLAMINE SECRETION BETWEEN OLMESARTAN AND ENALAPRIL
Authors: Koh Young Youp , Cho Byung Ryul , Lim Dong Yoon 
Published: January 2023

Objective:
The present study was designed to compare olmesartan, an angiotensin II receptor blocker (ARB) with enalapril, an angiotensin converting enzyme inhibitor (ACEI) in the suppressive effects on the secretion of catecholamines (CA) from the perfused model of the rat adrenal gland.

Design and Methods:
The adrenal gland was isolated and perfused with Krebs-bicarbonate. CA was measured directly by using the fluorospectrophotometer.

Results:
Both olmesartan (50 μM) and enalapril (50 μM) during perfusion into an adrenal vein for 90 min inhibited the CA secretory responses evoked by ACh (5.32 μM), DMPP (a selective neuronal nicotinic Nn receptor agonist, 100 μM), high K+ (a direct membrane-depolarizer, 56 μM), and McN-A-343 (a selective muscarinic M1 receptor agonist, 100 μM) in a time-dependent manner. Also, in the presence of enalapril or olmesartan, the secretory responses of CA evoked by veratridine (an activator of voltage-dependent Na+ channels, 100 μM), Bay-K-8644 (a L-type dihydropyridine Ca2+ channel activator, 10 μM), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor, 10 μM) were significantly reduced. Based on the same concentration (50 μM) of enalapril and olmesartan, for the CA release evoked by Ach, high K+, DMPP, McN-A-343, angiotensin II, veratridine, Bay-K-8644 and cyclopiazonic acid, the following rank order of inhibitory potency was obtained: olmesartan > enalapril. In the simultaneous presence of enalapril and olmesartan, Ach-evoked CA secretory responses were more strongly inhibited in comparison with that of enalapril- or olmesartan-treated alone.

Conclusion:
Collectively, these results demonstrate that both enalapril and olmesartan inhibit the CA secretory responses evoked by activation of both cholinergic and angiotensin II receptors stimulation as well as by direct membrane depolarization in the perfused model of the isolated rat adrenal medulla. When these two drugs were used in combination, their effects were enhanced, which may also be of clinical benefit. Based on concentration used in this study, it seems that the inhibitory effect of olmesartan on the CA secretion is more potent than that of enalapril.
PS-B03-7: MAGNESIUM SULPHATE TREATMENT DURING HYPERTENSIVE PREGNANCY IMPROVES MATERNAL BUT NOT FETAL OUTCOMES IN RATS
Authors: Scott Kayley , Olivera Sol , Peden Lara , McBride Martin W , Delles Christian , Graham Delyth 
Published: January 2023

Objective:
There has been a recent rise in the incidence of cardiovascular disease amongst women of child-bearing age and hypertensive disorders in pregnancy, in particular pre-eclampsia. Though it is frequently diagnosed, therapeutic interventions are lacking. Magnesium sulphate (MgSO4) is known to induce a vasodilatory effect via increased NO production and improved endothelial function and is currently used to prevent the progression to eclampsia and seizures from pre-eclampsia in the clinic. Magnesium homeostasis is also crucial during a healthy pregnancy and hypomagnesemia has been linked to cardiovascular disease. We hypothesised that MgSO4 may be used as a preventative therapeutic during hypertensive pregnancies in a rodent model of super-imposed pre-eclampsia.

Design and Methods:
Spontaneously hypertensive stroke prone (SHRSP) female rats were time mated. On gestational day (GD) 10.5 0.9% saline (SHAM, n = 10) or 750ng/kg/min of ANGII (n = 17) were administered via mini pump. A subset of ANGII and SHAM animals received daily 1% w/v MgSO4 drinking water from GD0.5 (n = 4/group; SHAM/ANGII+MgSO4). Blood pressure, cardiac function, and uteroplacental blood flow were measured by tail-cuff plethysmography and Doppler ultrasound pre-pregnancy (PP) and at GD6.5, 12.5, and 18.5. Urine samples were collected by metabolic cage at PP, GD6.5, and GD18.5 for measurement of proteinuria. Fetal and placental measurements were collected at sacrifice.

Results:
ANGII shows features consistent with SPE in humans via decreased stroke volume and elevated blood pressure alongside decreased fetal and placental weights vs SHAM (****p < 0.0001, **p < 0.01, *p < 0.05). Additionally, ANGII resulted in significantly altered fluid homeostasis and proteinuria vs SHAM (****p < 0.0001, ***p < 0.001, **p < 0.01). ANGII+MgSO4 showed a decrease in blood pressure vs ANGII (**p < 0.01). Treatment with MgSO4 had no significant effect on cardiac function, though there was a trend towards improvement in delta cardiac output. Neither ANGII nor additional MgSO4 altered indices of uteroplacental flow vs ANGII or SHAM. ANGII+MgSO4 exhibited a significant reduction in proteinuria vs ANGII (*p < 0.05) as well as improvements in fluid homeostasis. Both fetal and placental weights were significantly reduced in ANGII+MgSO4 vs SHAM (**p < 0.001) indicating a detrimental effect.

Conclusions:
These results suggest 1% w/v MgSO4 may be beneficial as a preventative therapeutic in pregnancies affected by super-imposed pre-eclampsia for maternal but not fetal outcomes. Further work is needed to elucidate the effects of MgSO4 in the context of hypertensive pregnancy.
PS-B03-8: ORAL CANNABIDIOL REDUCES ARTERIAL BLOOD PRESSURE DURING EARLY PHASE METABOLIC SYNDROME IN OLETF RATS
Authors: Wilson Jessica N , DiPatrizio Nicholas V , Ortiz Rudy M 
Published: January 2023

Objective:
Cardiovascular disease (CVD) is the leading cause of death in the U.S. and a primary outcome of metabolic syndrome (MetS). MetS is diagnosed by the presentation of at least 3 of the 6 conditions including abdominal obesity, elevated arterial pressure, and glucose intolerance ± insulin resistance. Identifying the root cause of these conditions individually is difficult but developing new treatments, which can ameliorate the multiple conditions of MetS has greater potential to reduce later-onset CVD. The benefits of cannabidiol (CBD) is widely recognized for potent anti-inflammatory and antioxidative properties, which may be cardioprotective during isolated risk factor conditions. However, these effects have not been examined during MetS conditions.

Design:
A cohort of 14-week-old Otsuka Long-Evans Tokushima Fatty (OLETF) rats were administered 175 mg CBD/kg by oral gavage for 5 weeks (CBD; n = 8). Animals were fed ad libitum and monitored alongside vehicle-treated OLETF (OLETF; n = 8) and vehicle-treated Long-Evans Tokushima Otsuka (LETO) rats, the lean-strain controls (LETO; n = 8). Rats were implanted with biotelemeters to chronically measure arterial pressure [DSI; HD-S10]. An oral glucose tolerance test (oGTT) was performed after 5 weeks of treatment.

Results:
CBD reduced arterial pressure within the first week of dosing (6 ± 1.4 mmHg or 4.1%; p < 0.05) and, after 5 weeks, by 9.7 ± 1.7 mmHg (6.5%; p < 0.05) from baseline. CBD blunted body mass gain and reduced abdominal adiposity by 39% (p < 0.0001) compared to untreated OLETF. Additionally, glucose absorption (AUCglucose 10 minutes after glucose bolus) was reduced 21% (p < 0.01) and enhanced uptake (slope 60 minutes to 120 minutes after glucose bolus) by 160% (p < 0.05). However, neither glucose response overall nor static fasting blood glucose were improved. On the other hand, insulin response (AUCinsulin) was reduced 77% (p < 0.0001) compared to OLETF, which ultimately reduced calculated insulin resistance index (IRI) of 79% (p < 0.0001). Moreover, CBD treatment reduced fasting plasma insulin by 76% compared to OLETF (p < 0.001). CBD decreased adiposity by 59% (p < 0.0001) associated with reduced plasma leptin.

Conclusions:
A chronic, high dose of CBD reduced the MetS-associated hypertension and other cluster factors. The renin-angiotensin-aldosterone system is a known driver of hypertension in humans with MetS and in the OLETF rat model and could be directly or indirectly modulated by CBD (analysis on-going). Collectively, CBD could be a novel and effective intervention strategy for early-stage hypertension and other metabolic risk factors associated with MetS.
PS-B04-1: ANTI-HYPERTENSIVE AND ANTI-PROTEIURIC EFFECTS OF MELINJO SEED EXTRACT IN THE RAT REMNANT KIDNEY MODEL
Authors: Tamura Yoshifuru , Morimoto Chikayuki , Nakagawa Takahiko , Shibata Shigeru 
Published: January 2023

Melinjo (Gnetum gnemon L.) is a fruit native to Indonesia and is considered as a healthy food. Melinjo resveratrol (MjR) is a resveratrol derivative extracted from the melinjo seed. Interestingly, recent literatures have documented that MjR exhibits the angiotensin converting enzyme inhibitory activity. Hence, we hypothesized that MjR exhibits beneficial effects in the chronic kidney disease. In order to test our hypothesis, MjR was administered in the rat remnant kidney (RK) model. Rats were divided into three groups: sham operated rats (SHAM, n = 4), untreated remnant kidney rats (RK, n = 5), RK rats treated with MjR 300 mg/kg/day (RK + MjR, n = 5). The rats were sacrificed at twelve weeks.
Blood pressure and urinary protein levels significantly increased whereas creatinine clearance (CCr) significantly descread in the RK group compared to the SHAM group at twelve weeks. MjR significantly reduced systolic blood pressure (108 ± 2 vs. 147 ± 2 mmHg, p < 0.05) as measured by tail-cuff methods. Urine protein excretion was significantly ameliorated by MjR compared with that in RK (79.8 ± 54.8 vs. 269 ± 87.5 mg/day, p < 0.0015). Although Ccr was not altered in RK + MjR compared with RK rats, histological evaluation revealed that the glomerular sclerosis was attenuated in RK + MjR group. Podocytes in the RK rats showed increase in desmin, a marker of podocyte injury, which was alleviated with the administration of MjR.
In conclusion, MjR reduced blood pressure, proteinuria and glomerular damage in the RK rats. These data suggest that MjR may mitigate the progression of chronic kidney disease, which needs further confirmation.
PS-B04-2: DIMETHYL FUMARATE IMPROVES RAT VIABILITY WITH SUPPRESSION OF BLOOD PRESSURE, TGF-B1 EXPRESSION AND RENAL DAMAGE IN DAHL/SALT SENSITIVE RATS
Authors: Ito Satoyasu , Tsujino Takeshi 
Published: January 2023

Objective:
Cardiovascular disease and chronic kidney disease are known to adversely affect each other. Inflammation is commonly involved in both diseases. Dimethyl fumarate (DMF) is an FDA-approved antioxidant and anti-inflammatory agent. DMF triggers an anti-inflammatory response by activating Nfr2, which is associated with NFkB signaling. The purpose of this study was to investigate the effect of DMF on Dahl/Salt sensitive(DS) rats.

Methods:
Six-week old DS rats were divided into the following three groups, namely the control group, the high-salt (HS) group, and the HS +DMF(HS+DMF) group. The HS and HS+DMF groups were given a high-salt diet (8%NaCl) from 6 weeks of age. The HS+DMF group was orally administered DMF (90 mg/kg/day) from 6 to 15 weeks of age. The systolic blood pressure (SBP) was measured using a noninvasive tail-cuff method every 2 weeks. Renal damage was evaluated with histopathologic analysis using PAS and Massons trichrome staining. Renal expression of Transforming Growth Factor-beta1 (TGF-b1) mRNA was evaluated with reverse transcription-polymerase chain reaction (RT-PCR).

Results:
DMF significantly improved overall survival rate of DS rats that had been shortened with HS. SBP increased in the HS group compared to the control groups, and DMF suppressed this change. DMF also improved the renal tubule damage and fibrosis confirmed in the HS group by histopathological analysis. Furthermore, renal TGFb1 mRNA expression was increased in the HS group, and it was suppressed by DMF.

Conclusion:
This study suggests that DMF improved overall survival rate of DS rats through the organ-protective effect.
PS-B04-12: DEVELOPMENT OF VACCINE AGAINST CONNECTIVE TISSUE GROWTH FACTOR TO PREVENT THE PROGRESSION OF RENAL FIBROSIS
Authors: Nakayama Takashin , Azegami Tatsuhiko , Hayashi Kaori , Hishikawa Akihito , Yoshimoto Norifumi , Nakamichi Ran , Sugita Erina , Itoh Hiroshi 
Published: January 2023

Objective:
Hypertension is closely related with chronic kidney disease (CKD); Hypertension and CKD can cause and exacerbate each other, forming a vicious cycle. There is a critical need for efficient treatment of CKD. Renal fibrosis is a final common pathway to end-stage renal disease, and connective tissue growth factor (CTGF) is a well-recognized central profibrotic factor in fibrosis of various organ systems. Here, we developed a novel peptide vaccine against CTGF to prevent the progression of renal fibrosis.

Design and method:
Among sequences of CTGF, the sequence common to mice and humans in the interaction region with transforming growth factor-β; (TGF-β;) and bone morphogenic proteins was selected as the epitope for the vaccine. The efficacy of this vaccine was verified in two renal fibrosis models using male C57BL/6J mice: adenine-induced CKD and unilateral ureteral obstruction (UUO) models. Moreover, the functions of CTGF vaccine-elicited IgG antibodies were evaluated in an in vitro study.

Results:
Three immunizations with this CTGF vaccine at 2-week intervals elicited serum IgG antibodies specifically binding to human full-length CTGF, and the antigen-specific antibody titers were maintained at high level for > 30 weeks. In adenine-induced CKD model, histological analyses showed that immunization with the CTGF vaccine significantly attenuated renal interstitial fibrosis compared to the vehicle treatment (8.5 ± 0.8% vs 12.3 ± 0.8%; P < 0.01). The CTGF vaccination also suppressed the increased mRNA expressions of collagen 1α and α-smooth muscle actin (α-SMA) in kidney tissue samples. Moreover, vaccinated mice showed lower levels of serum urea nitrogen (UN) and creatinine and lower urine albumin-creatinine ratio compared with vehicle-treated mice (UN: 77.7 ± 5.0 vs 104.0 ± 6.8 mg/dL; P < 0.01. creatinine: 0.42 ± 0.02 vs 0.51 ± 0.04 mg/dL; P = 0.06. albumin-creatinine ratio: 74.7 ± 13.8 vs 132.0 ± 15.3 μg/mg; P < 0.05). In UUO model, the CTGF vaccination also ameliorated the expansion of the interstitial fibrotic areas (7.7 ± 0.4 vs 9.8 ± 0.7%; P < 0.05). In an in vitro study, CTGF vaccine-elicited IgG antibodies efficiently suppressed CTGF-induced- and TGF-β;-induced α-SMA expression in cultured kidney fibroblasts.

Conclusions:
The CTGF vaccine has the potential to prevent the progression of renal fibrosis and delay the deterioration of renal function with a low frequency of administration. Thus, this CTGF vaccine could be a promising preventive strategy for CKD patients.
PS-B05-9: ADVANCED MATERNAL AGED MOUSE MODEL SHOWED FETAL GROWTH RESTRICTION AND WOULD BE A MODEL FOR DOHAD
Authors: Nakazato Rei , Mii Akiko , Kamijo Natsumi , Tani Takashi , Arakawa Yusuke , Sakai Yukinao , Iwabu Masato 
Published: January 2023

Backgrounds:
The number of advance-aged pregnancies, defined as those over 35 years of age, has been increasing in developed countries due to tendency to marry later with women's social advancement and assisted reproductive technology. Furthermore, in Japan, the incidence of hypertensive disorders of pregnancy over 40 years of age is as high as approximately 8%, which have a high rate of premature births and low birth weight, and fewer nephrons. Recently, based on the developmental origins of health and disease (DOHaD) hypothesis, it has been recognized that the risk of developing hypertension, proteinuria and renal failure in the future is increased in aged pregnancies. However, the detailed mechanism is uncertain.

Methods:
Female ICR mice of 6 to 10 months (Advanced maternal age, AMA group) and of 10 to 12 weeks (Control; CON group) were mated with males of 10 to 16 weeks. Blood pressure during pregnancy on day 7 and 14 was measured in both groups (n = 4, n = 4). The pups born in both groups (AMA, n = 4–13; CON, n = 10–16) were weighed at postnatal day 0, a week, 4 weeks, and 8 weeks of age. Blood pressure (n = 7, n = 3) at 8 weeks of age was measured using the tail-cuff technique. The results were compared using the Mann-Whitney U test.

Results:
There was no difference in blood pressure during pregnancy on day 7 and day 14 in both groups. In the AMA mouse model, the weights of postnatal day 0 pups were significantly lower (AMA vs. CON, 1.66 ± 0.22 g vs. 1.9 ± 0.22 g, P = 0.006). However, no difference was found between the two groups at a week and 4 weeks. Conversely, the body weights of the AMA model were significantly higher at 8 weeks of age (AMA vs. CON, 47.7 ± 3.43 g vs. 45.4 ± 2.8 g, P = 0.041) and the systolic blood pressure in the AMA group tended to be higher.

Discussion/Conclusion:
In the present study, the AMA mouse model induced fetal growth restriction and subsequently showed catch-up growth. Furthermore, their pups’ weights were significantly higher and elevated blood pressure was observed at adult age. While previous animal models of DOHaD have been mainly based on studies of dietary restriction, chemical exposure, and preeclampsia, this model showed similar symptoms to DOHaD models.