bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-BPR02-5: A CASE OF JUVENILE-ONSET HYPERTENSION WITH A GIANT LEFT ANTERIOR THORACIC ARTERIOVENOUS FISTULA
Authors: Nakatani Yoshihisa , Okada Nobutaka , Shimizu Kazuyuki , Miyake Sayoko , Kobayashi Norihiro , Nakano Yukihito , Arima Shuji
Published: January 2023

(Case) 3X years old male:

(Current medical history) In school days he had been aware of a subcutaneous mass in the left anterior chest and from the same period he often had severe headache but left it unattended. He was diagnosed with hypertension at the age of 20 years old and with giant left anterior thoracic arteriovenous fistula. He was operated but could not completely remove it. Then he has performed vascular embolization at five times. He was hospitalized for the sixth embolization in 202x due to increased arteriovenous fistula. A high blood pressure (178/97 mmHg) was observed at admission and the sixth embolization of the left thoracic shoulder lateral thoracic and internal thoracic artery was performed the day after hospitalization. After embolization he was discharged one week later. However the high blood pressure continued even after discharge and the headache did not improve so he was referred to our department. His father and mother and grandparents and brothers had high blood pressure. It may be suggesting familial and juvenile hypertension. Blood pressure of upper limb left 171/108 mmHg / right 178/112 mmHg (not significantly difference) ABI left 1.13 / right 1.10 and PWV left 2069 / right 1804 cm/s and arteriosclerosis was remarkable. CT imaging showed no adrenal enlargement but multiple kidney stones. Serum Ca and Mg levels were in the normal range and no high ARR84 (renin/aldosterone ratio) was observed. Ask-Mark syndrome was negative. He started taking amlodipine 5 mg for hypertension and then increased the dose and exchanged NifedipineCR 40 mg. After that carvedilol 10 mg was added and the blood pressure decreased to 120–130 / 70–80 mmHg and the control became good. Blood pressure showed a tendency to increase in eight months after the sixth embolization again and at the same time CT showed a slight increase in arteriovenous fistula.

Conclusion:

We experienced a case of juvenile-onset hypertension in which blood pressure could be controlled using three antihypertensive drugs in addition to the treatment of giant thoracic arteriovenous fistula embolization. The cause of juvenile onset and increased blood pressure was thought to be related to the effects of congenital battlement and longitudinal arteriovenous fistula which do not exhibit pulmonary circulation or circulatory system. Conventionally congenital battlement / longitudinal arteriovenous fistula has a mild left ventricular load and almost no increase in blood pressure has been reported. However it may be possible the left ventricular load became larger and caused hypertension because of the huge thoracic arteriovenous fistula.
PS-BPR03-2: A RARE CASE OF TAKAYASU ARTERITIS INDUCED RENOVASCULAR HYPERTENSION IN A PATIENT WITH CROHN DISEASE
Authors: Nagayama Shohei , Suzuki Shota , Nakayama Izumi , Ozawa Moe , Kawano Rina , Kamiyama Akina , Oki Yuki , Fujiwara Akira , Saka Sanae , Iwamoto Tamio , Hirawa Nobuhito
Published: January 2023

Takayasu arteritis (TA) is chronic inflammatory arteritis affecting large vessels, predominantly the aorta and its main branches. Vascular inflammation occurs wall thickening, fibrosis and stenosis. Arterial stenosis due to TA often causes secondary hypertension. Crohn disease (CD) is chronic granulomatous, inflammatory gastrointestinal disease, It can cause various extraintestinal complications. A few case reports and small case series reported complications of TA and CD. In recently, there are several reports that TA are revealed in patients treated with anti-tumor necrosis factor - alpha antibody for CD. We report a 18 years old male in whom TA was manifested mainly by severe hypertension and proteinuria after infliximab administration for CD.

He was diagnosed with CD at the age of 17. He had a great fever and high CRP levels (6.55 mg/dl), and endoscopic examination revealed multiple longitudinal ulcers in the large intestine and ileum. Although, he was treated with adalimumab and 5 -aminosalicylic acid, fever and CRP levels did not improve, Infliximab was administered. Following infliximab administration, his laboratory data revealed renal impairment (blood urea nitrogen level: 13 mg/dl, creatinine level: 1.28 mg/dl), proteinuria (10.0 g/gCr) and he had severe hypertension (about 190/100 mmHg). Both, his plasma aldosterone concentration (PAC) (RIA) and plasma renin activity (PRA) were significantly high (PAC: 798 pg/ml. PRA: 66.2 ng/ml/hr). In addition, magnetic resonance angiography and radioisotope renogram findings revealed stenoses of the right renal artery. Although, a simple CT scan performed 5 months earlier showed no abnormalities in both kidney, contrast-enhanced CT revealed stenoses of the right renal artery, superior mesenteric artery, right renal atrophy, and left renal enlargement. The 99mTc-DTPA Renography reveled severe right renal dysfunction (GFR 14.67/61.21 ml/min). Based on these findings, patient was diagnosed with TA induced renovascular hypertension complicated with CD, and oral administration of prednisolone from 1 mg/kg/day and antihypertensive drugs (amlodipine, doxazosin, and spironolactone) was started. After 14 days treatment, his blood pressure was about 170/90 mmHg. Finally, losartan was administered, his blood pressure was reduced to 120∼150/70∼90 mmHg, and no changes in his serum creatinine levels was observed. We report with a review of the literature.
PS-BPR03-6: A CASE OF COARCTATION OF THE AORTA THAT DOPPLER ULTRASOUND WAS USEFUL FOR INVESTIGATING THE CAUSE OF ADOLESCENT REFRACTORY HYPERTENSION
Authors: Morikawa Takashi , Kitabayashi Chizuko , Matsuki Aoi , Kadosawa Keita , Sakata Yuko , Nagatsuji Katsushi , Yamazaki Daisuke , Hamada Masahiro , Yamagami Keiko , Bito Yasuyuki , Konishi Yoshio
Published: January 2023

A 17-year-old female was referred to our department with hypertension refractory to medical treatment. When she presented to the otolaryngologist 3 years earlier for dizziness, her systolic blood pressure was 170 mmHg. On physical examination, her blood pressures in right and left arms were 193/99 and 196/106 mm Hg, respectively. Also, a systolic ejection murmur of grade 2/6 was present at the left upper sternal border. She was prescribed cilnidipine 20 mg/day and nifedipine CR 40 mg/day, but her blood pressure was 160/90 mmHg. Plasma renin activity was 5.2 ng/ml/h, and serum aldosterone was 210.4 pg/ml, so renovascular hypertension was suspected. However, contrast-enhanced 3-dimensional computed tomography (3DCT) of the both renal arteries showed no stenosis. On the other hand, renal doppler ultrasound revealed a slow rise in systolic blood flow waveform in both renal arteries and intrarenal arteries. This indicates that the vessel upstream of the measurement site is stenotic. The similar blood flow waveform was observed in the abdominal aorta, suggesting aortic stenosis upstream of the abdominal aorta. 3DCT of the thoracic aorta revealed a significant coarctation of the thoracic aorta distal to the origin of the left subclavian artery. We diagnosed her as coarctation of the aorta, and performed a descending aortic replacement procedure. As a result, her blood pressure decreased to 130/80 mmHg under cilnidipine 20 mg/day. The waveform of both renal arteries, intrarenal arteries and abdominal aorta became a normal pattern by doppler ultrasound. Hypertension in adolescent is uncommon. As secondary causes are more commonly found in this age group than in older adults, aortic coarctation should be considered. Early diagnosis and treatment are essential for the prevention of morbidity and mortality from premature cardiovascular complications. Here, we described a case of coarctation of the aorta that doppler ultrasound was useful for investigating the cause of adolescent refractory hypertension.
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-B05-2: ANALYSIS OF SHORT-TERM CARDIOVASCULAR AND RENAL DISORDERS IN MICE WITH CARDIO-RENAL DAMAGES
Authors: Noguchi Kazuyuki , Ishida Junji , Muromachi Naoto , Akiyama Tomoki , Kim Jun-Dal , Usui Joichi , Yamagata Kunihiro , Fukamizu Akiyoshi
Published: January 2023

Chronic kidney disease (CKD) and cardiovascular disease (CVD) coexist often and pose a risk for disease progression. In recent years, a concept of “cardio-renal syndrome” has been proposed, in which disruption of cardio-renal homeostasis causes mutual harm. The renin-angiotensin system, sympathetic nervous system, and inflammation are involved in the cardiorenal axis, but the details of underlying molecular mechanisms have not been elucidated. We have previously reported that a heart failure model (ANS mice) subjected to simultaneous angiotensin II (A), unilateral nephrectomy (N), and salt (S) administration developed cardiac dysfunction, renal dysfunction, and proteinuria at 4 weeks post-treatment and may serve as a model for cardio-renal coupling pathophysiology. In the present study, we analyzed renal and cardiovascular lesions in ANS mice at week 1 of treatment. Interestingly, ANS mice exhibited cardio-renal lesions including cardiac fibrosis, aortic atherosclerosis, proteinuria, and tubular damage even at the short intervention period of 1 week (under submission). These results indicate that the ANS mice may be a useful tool for the analysis of the early pathophysiology of cardio-renal syndrome.
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.
PS-B06-2: IN VIVO MYOCARDIAL EFFECTS OF INTRAPERITONEAL ARGLABIN VIA NLPR3 INFLAMMASOME AND MAPK/IKKB;/NFKB PATHWAYS
Authors: Bisht Khushboo , Arya Dharam Vir Singh , Verma Vipin Kumar , Abdullah Zia , Ray Ruma , Narang Rajiv , Nag Tapas Chandra , Bhatia Jagriti
Published: January 2023

Introduction:

Myocardial injury is a consequence of multiple underlying events that lead immune response by activated immune cells. Oxidative stress triggers an inflammatory cascade and apoptosis, this exacerbates cardiac injuries and dysfunction. Arglabin is a sesquiterpene lactone, an anticancer compound shown to have potential anti-diabetic effects in in vivo model.

Methods:

Male Wistar Rats in the 6 out of 9 groups were pre-treated with different doses (2.5 μg/kg, 5 μg/kg and 10 μg/kg of Arglabin) for 21 days. other 3 groups were normal control, vehicle and isoproterenol control. On 22nd day, isoproterenol was injected to induced myocardial injury (85 mg/kg/day). Normal control and isoproterenol control groups. Histopathological examination, electron microscopy, biomarkers (cTnI and LDH), cardiac parameters, oxidative stress (MDA, GSH, SOD, and CAT), inflammatory mediators (IL-6, IL-1β;, and TNF α), and apoptotic markers (BAX, Bcl2, and caspase-3) were evaluated.

Results:

Histopathological examination revealed increased neutrophilic infiltration in arglabin pretreated groups that correlated with electron microscopic findings. increased activity of IL-6, IL-1β;, TNFα, Caspase-1, caspase-3 and BAX was found in different pre-treated group. increased JNK expression was observed in arglabin pre-treated groups (2.5,5,10). altered expression of NFκB, P38, pP38 and IKKβ; were observed.

Conclusion:

Arglabin administration altered myocardial structure and modulated myocardial function via NLRP3 and MAPK pathway. Consideration regarding cardiovascular adverse effects must be undertaken when exploring other potential role of arglabin. Also, continuous cardiovascular monitoring is suggested for those on anti-cancer treatment with arglabin.
PS-B07-1: BRAIN-TARGETED MECHANICAL INTERVENTION USING PASSIVE HEAD MOTION CAN BE ANTIHYPERTENSIVE
Authors: Sakitani Naoyoshi , Maekawa Takahiro , Yoshino Daisuke , Takano Kouji , Shinohara Keisuke , Kishi Takuya , Tomiyasu Koji , Ogata Toru , Tsuchimochi Hirotsugu , Saito Shigeyoshi , Yoshino Kohzoh , Funamoto Kenichi , Shinohara Masahiro , Nagao Motoshi , Sawada Yasuhiro
Published: January 2023

Objective:

Reproduce the antihypertensive effect of physical exercise by applying mechanical intervention.

Design and method:

We conducted animal experiments in which we reproduced mechanical accelerations generated in the head during treadmill running at a moderate velocity. We performed in vitro experiments using cultured cells to determine what type of mechanical force was responsible for the antihypertensive effect of mechanical intervention. We carried out clinical studies to validate the clinical relevance of our findings.

Results:

Passive head motion in hypertensive rats, which reproduced the mechanical accelerations generated in their heads during treadmill running at a moderate velocity, decreased the expression of angiotensin II type 1 receptor (AT1R) in astrocytes in the rostral ventrolateral medulla (RVLM). This decrease resulted in lowering their blood pressure. Passive head motion generated interstitial fluid movement, which was estimated to exert shearing forces with an average magnitude of < 1 Pa on the cells in the rat medulla. Application of fluid shear stress of relevant magnitudes decreased the AT1R expression in cultured astrocytes, but not in neuronal cells. Furthermore, interference with interstitial fluid movement by hydrogel introduction in the RVLM of hypertensive rats eliminated the ability of passive head motion and treadmill running to decrease their blood pressure and AT1R expression in the RVLM astrocytes. Consistent with these results from animal experiments, vertically oscillating chair riding by hypertensive adult humans, which reproduced the mechanical accelerations generated in their heads during light jogging, lowered their blood pressure.

Conclusion:

Brain-targeted mechanical intervention can be antihypertensive by modulating the function of RVLM astrocytes through interstitial fluid shear stress.
PS-B07-2: EXERCISE TRAINING PREVENTS HIGH FRUCTOSE-INDUCED HYPERTENSION AND RENAL DAMAGES IN DAHL SALT-SENSITIVE RATS
Authors: Xu Lusi , Hu Gaizun , Kohzuki Masahiro , Ito Osamu
Published: January 2023

Background:

High fructose diet (HFr) causes metabolic syndrome, and HFr-induced hypertension and renal damage are exaggerated in Dahl salt-sensitive (DS) rats. Exercise training (Ex) have antihypertensive and renal protective effects in rats fed HFr, but these effects of Ex are weak in DS rats fed a high-salt diet. This study thus examined the effects of Ex on DS rats fed HFr.

Methods:

Male DS rats were divided into three groups. The control group was fed a control diet, both the HFr group and the HFr-Ex group were fed a HFr (60% fructose). The HFr-Ex group also underwent treadmill running (20 m/min, 60 min/day, 5 day/ week). After 12 weeks, renal function, histology, and renin-angiotensin system (RAS) were examined.

Results:

HFr increased blood pressure, urinary albumin, and creatinine clearance, and Ex inhibited these increases. HFr induced glomerular sclerosis, podocyte injury, afferent arteriole thickening, and renal interstitial fibrosis, and Ex ameliorated them. HFr reduced plasma renin activity, and Ex further reduced the activity. HFr also increased the expression of angiotensinogen, renin, angiotensin converting enzyme (ACE), and angiotensin II type1 receptor (AT1R), and Ex restored the ACE expression to the control levels. HFr decreased the expression of ACE2, angiotensin II type2 receptor (AT2R), and Mas receptor (MasR), and Ex restored the ACE2 and MasR expressions to the control levels and further decreased the AT2R expression. HFr increased the ACE activity and decreased the ACE2 activity, and Ex restored these activities to the control levels.

Conclusion:

Ex prevents HFr-induced hypertension and renal damages in DS rats. The changes in renal RAS may be involved in the mechanism of the antihypertensive and renal protective effects of Ex.
PS-B07-3: ANGIOTENSIN I CONVERTING ENZYME INHIBITORY PEPTIDES DERIVED FROM KATSUOBUSHI
Authors: Seki Eiji
Published: January 2023

Purpose:

Antihypertensive components are typically assessed by screening based on in vitro results; however, since intestinal absorption is closely involved in the antihypertensive mechanism of action, we attempted to analyze the absorption of bonito derived peptides, which have been found to have antihypertensive effects in animal experiments.

Methods:

The intestinal tracts of rats, 7 week old male SDrats, were excised after performing cervical dislocation. Incisions 5.5 cm were quickly made into the jejunum, one side was ligated and inverted, and after injecting 1 mL reaction solution, the other side was ligated to create an inverted sack. The sack was then quickly placed in 30 mL of the reaction solution, antihypertensive amount: KBP 0.3 mg/per animal and synthetic peptides: each 0.25 mM, and left to react for 30 min at 37°C after which the inverted sack was removed and washed gently with physiological saline before recovering all the internal fluid. Liquid chromatography tandem mass spectrometry LC/MS/MS was used for analysis and the intestinal fluid samples were measured after examining pretreatment and measurement conditions.

Results:

Pretreatment conditions involved adding 5 μL water, 5 μL IS L-Leu-D-Leu, and 5 μL of 20% sulfosalicylic acid to a 50 μL intestinal fluid sample, stirring the sample, transferring 0.22 μm to a centrifugal filter, performing centrifugation for 3 min at 20000 g and 4°C and then injecting the filtrate into the LC/MS/MS system. LC conditions included a 1.7 μL ACQUITY UPLC BEH C18 column; 2.1, 50 mM, 0%-100% acetonitrile/0.1% TFA linear gradient elution in the mobile phase. Based on the above analysis conditions, the GW, AW, VW, MW, IW, LW, and WL values ng/mL of KBP in the reaction solution were 34.0, 4.64, 7.11, 1.28, 12.7, 4.57, and 0.923, respectively, and 53.2, 3.92, 6.02, 1.10, 8.76, 5.76, and 0.785, respectively. Values for the reaction solution of additive-free peptides serving as a base were estimated at 13.5, 1.09, 2.06,0.350, 5.54, 1.72, and 0.189, respectively. The calibration curve range was set at 0.200–1000ng/ mL.

Conclusion:

The intestinal membrane permeability of dried bonito-derived dipeptides, which have an antihypertensive effect in vivo, suggests that dipeptides absorbed from the intestinal membrane may have an antihypertensive effect.
PS-B07-7: MACHINE LEARNING CLASSIFICATION OF CORONARY HEART SYNDROME BASED ON ELECTROCARDIOGRAM IMAGE USING CONVOLUTIONAL NEURAL NETWORK ALGORITHM
Authors: Fajar Rifaldy , Selena Maria , Alorra Zoya
Published: January 2023

Background and Aim:

Electrocardiogram (ECG) is one of the most important examination models used to diagnose various abnormal heart rhythms. An EKG records the electrical activity of the heart through wires and electrodes that are attached to the skin of the arms, legs, and chest wall. Early examination of heart defects can improve quality of life through appropriate treatment. One of the abnormalities in the heart is coronary heart disease. CHD is a heart disease that is mainly caused by the narrowing of the coronary arteries due to atherosclerosis or spasm or a combination of both. In this study, a system was designed to classify coronary heart disease from the results of ECG images.

Methods:

The study consisted of several stages, starting with the collection of ECG image data for cardiac abnormalities which were used for training images and testing images. The next step is pre-processing using a grayscale process to show the intensity value. Furthermore, at the segmentation stage, a thresholding process is used which aims to divide the image into two parts, namely between the object and the background by forming a binary image. The next stage is the process of taking feature values from the segmentation results using Invariant Moment. The final stage is classification using the Convolutional Neural Network. The data used in this study are images obtained from Beecardia physiobank. There are four classifications of images processed in this system, namely Normal, Asymptomatic, Angina Pectoris, and Acute Myocardial Infarction. The amount of data used is 126 where the image is divided into two, namely, 101 training data and 25 testing data.

Results:

The Convolutional Neural Network method is able to classify coronary heart disease from the results of ECG images very well. The results of the classification process for coronary heart disease from the results of ECG images are able to achieve an accuracy of 92%.

Conclusion:

The classification system can perform its performance well, as evidenced by the percentage obtained, including a height exceeding 90%. Suggestions for the future, more training data can be used so that at the time of testing, the test data can get higher accuracy.
PS-B07-9: THE EFFECT OF ROUTINE PHYSICAL ACTIVITY TOWARD THE AORTIC WALL AREA IN RAT MODEL OF TYPE 2 DIABETES MELLITUS
Authors: Alfaruqy Maulida Abdillah , Pramaningtyas Miranti Dewi
Published: January 2023

Background:

The damages in pancreatic b-cell as one of the main pathophysiologies of type 2 diabetes mellitus (T2DM) may result in hypoinsulinemia and hyperglycemia. Physical activity plays an important role in the comprehensive management of diabetes mellitus. This study aimed to understand the effect of routine physical activity on the aortic wall area of T2DM rat model.

Methods:

This study is an animal model experimental research with a post-test only control group to measure the wall area of the abdominal aorta in diabetic rats after routine physical activity. Induction of T2DM in male Sprague Dawley rat was done by injecting streptozotocin 35 mg/kg intraperitoneally. The diabetic rats were divided into two groups: the first group get physical activity and the second group was not. The control was represented by a group that receive citrate buffer injection. A routine physical activity in low to moderate intensity is given using a special rat treadmill five times a week for nine weeks with a gradual rising of speed at 5–20m/minute for a maximum of 60 minutes. The rat abdominal aorta was stained by hematoxylin-eosin and the wall area was measured by ImageJ.

Results:

The mean of the wall area in diabetic rats with exercise is 452436.60(+42375.92) um2, in diabetic rats without exercise is 35998.81(+34724.68) um2, and in the control group is 434595.83(+34724.68) um2. The statistical analysis using the Kruskal-Wallis test shows no significant difference between the three groups (p = 0.052).

Conclusion:

In conclusion, diabetic rats with routine physical activity have a wider abdominal aorta wall area, but it is not statistically significant.