bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-BPR03-8: MALIGNANT HYPERTENSION WITH ACUTE KIDNEY INJURY AND THROMBOTIC MICROANGIOPATHY SUCCESSFULLY TREATED WITH ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR
Authors: Hishida Erika , Imai Toshimi , Nagata Daisuke 
Published: January 2023

Background:
Malignant hypertension is a disease characterized by severe hypertension and multi-organ damage. Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor (ARNi), has already demonstrated the superiority of reducing blood pressure versus olmesartan in patients with hypertension. ARNi has also been shown to improve cardiac biomarkers, cardiac remodeling, and prognosis in patients with heart failure, and a new AHA/ACC/HFSA guideline (2022) redefined to recommend ARNi as first-line renin-angiotensin-system inhibitors (class 1a) in patients with HFrEF (heart failure with reduced ejection fraction). However, the evidence about the efficacy and safety of ARNi in end-stage renal disease (ESRD) patients undergoing hemodialysis has been limited.

Presentation:
A 23-year-old man with no prior medical history was admitted to the previous hospital with severe hypertension (blood pressure 224/159 mmHg) associated with acute kidney injury (BUN 228.5 mg/dl, serum creatinine 25.50 mg/dl) and was referred to our hospital with the initiation of hemodialysis. He was also complicated with hypertensive heart failure with a preserved ejection fraction (NT-proBNP 172113 pg/ml). Blood test results also revealed thrombocytopenia (platelet 11.9 x 103/μL), hemolytic anemia (hemoglobin 7.4 g/dl, LDH 1076 U/L, haptoglobin < 10 mg/dl), and schistocyte on the blood smear, which was suggestive of thrombotic microangiopathy. His blood cell counts and serum LDH levels improved after antihypertensive treatment. Secondary hypertension, such as primary aldosteronism, Cushing's syndrome, pheochromocytoma, and renal artery stenosis, was deniable by further examination. The elevated levels of renin (65.5 ng/ml/hr) and aldosterone (685 pg/ml) were consistent with malignant hypertension. Serum antibody tests for screening of autoimmune disease were all negative. Renal biopsy revealed findings of malignant nephrosclerosis: glomerular collapse, glomerulosclerosis, endothelial swelling, and media thickening of the arteries. Oliguria recovered during the clinical course; however, his renal function did not fully recover. An arterio-venous fistula was created, and maintenance hemodialysis two times per week was continued during hospitalization. Even though his dry weight was adjusted to normal by repeated dialysis, his blood pressure was poorly controlled to systolic blood pressure of 160–170 mmHg by calcium channel blockers, angiotensin II receptor blocker (ARB), and alpha/beta-blockers. After switching from ARB to ARNi by increasing the dose to a maximum of 400 mg, his systolic blood pressure improved to 130–140 mmHg and was stable throughout the day, assessed by ambulatory blood pressure monitoring.

Conclusion:
Through our experience, it is conceivable that ARNi may be helpful in the settings of resistant hypertension in ESRD patients undergoing hemodialysis.
PS-BPR03-10: A CASE OF A WOMAN WITH IGA NEPHROPATHY PRESENTING DURING PREGNANCY
Authors: Yasuda Marie , Kanda Takeshi , Mito Asako , Arata Naoko , Itou Hiroshi 
Published: January 2023

Background:
Pregnancy has an influence on autoimmune diseases course and many autoimmune diseases go into remission during pregnancy. The details of the autoimmune mechanism of IgA nephropathy have not been elucidated. The disease activity of IgA nephropathy commonly is stable during pregnancy, however, IgA nephropathy is at high risk of pregnancy complications even if renal function is preserved, and prevention of pregnancy complications are important in pregnant woman with IgA nephropathy.

Case:
A 29 year-old woman, gravida 2, para 0, no history of abnormal urine analysis before pregnancy, presented preeclampsia at 32 weeks pregnancy, and an emergency cesarean section was performed at 32 weeks and 5 days pregnancy. After delivery, microscopic hematuria persisted. Renal biopsy was performed 1 year and 9 months after delivery, and IgA nephropathy was diagnosed. Tonsillectomy was performed for IgA nephropathy, and the patient's renal function did not deteriorate during the follow-up period. In the second pregnancy, low-dose-aspirin was administered from the first trimester, and full term infants delivered without any pregnancy complications.

Conclusion:
IgA nephropathy can become apparent in pregnancy. Postpartum evaluation of urinalysis is important for the early detection of the primary renal disease. In pregnant woman with IgA nephropathy, stabilization of the disease state and administration of low-dose aspirin are very important for outcome of pregnancy and maternal renal prognosis.
PS-B03-5: HIGH-DOSES OF LOSARTAN RATHER ENHANCE CATECHOLAMINE SECRETION FROM THE PERFUSED ADRENAL GLAND
Authors: Koh Young Youp , Cho Byung Ryul , Lim Dong Yoon 
Published: January 2023

Objective:
Previously, we have found that Losartan (5∼50 μM), an AT1 receptor blocker, dose-dependently inhibits secretion of catecholamines (CA) evoked by cholinergic and angiotensin II (Ang II) receptor stimulation from the perfused rat adrenal medulla. The aim of the present study was to examine the characteristic effects of high-dose losartan on the CA secretion from the isolated perfused rat adrenal gland, and also to establish its mechanism of action.

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

Results:
The perfusion of high-dose losartan (150 ∼ 600 μM) into an adrenal vein for 90 min resulted in great increases in CA secretions evoked by acetylcholine in a dose-dependent fashion. Also, losartan (300 μM) enhanced the CA release evoked by Ang II, high K+ and DMPP (a selective nicotinic receptor agonist), McN-A-343 (a selective muscarinic M1 receptor agonist). Also, in the presence of losartan (300 μM), the CA secretory responses to veratridine (a selective Na+ channel activator), Bay-K-8644 (a Ca2+ channel activator), and cyclopiazonic acid (a cytoplasmic Ca2+-ATPase inhibitor) were significantly potentiated, respectively. The facilitatory CA-releasing effect of Ach evoked by high-dose losartan (300 μM) was time-dependently depressed by pretreatment with nifedipine (Ca2+ channel blocker), while not by pretreatment with sodium nitroprusside (an NO donor). High-dose olmesartan (150 ∼ 600 μM), one of ARBs, also potentiated Ach-evoked CA release in time-dependent fashion. However, in the simultaneous presence of losartan (300 μM) and CGP42112 (an AT2 receptor agonist), the facilitatory responses of losartan on the CA secretion evoked by ACh were rather significantly reduced in comparison with that of losartan-treatment alone. Conclusion: Conclusively, these results demonstrate that high-dose losartan can potentiate the adrenomedullary CA secretion in a calcium-dependent fashion. It seems that this facilitatory effect of high-dose losartan may be mediated by activation of the Ca2+ influx through L-type Ca2+ channels into adrenomedullary cells without inhibition of NO synthesis, which seems to be relevant to AT2 receptor blockade. It also suggests that high-dose ARBs may be a risk factor in causing hypertensive response.
PS-B03-9: EPLERENONE PREVENTS CARDIAC FIBROSIS BY INHIBITING ANGIOGENESIS IN UNILATERAL URINARY OBSTRUCTION RATS
Authors: Chang Yi , Ben Ying , Li Hui , Shimosawa Tatsuo , Xu Qingyou 
Published: January 2023

Objective:
Cardiovascular disease constitutes the leading cause of mortality in patients with chronic kidney disease (CKD), which is termed cardiorenal syndrome type 4 (CRS-4). The aim of our experiments was to clarify the relationship between angiogenesis and endothelial-mesenchymal transition (End-MT) and the the development of pathological cardiac remodeling and fibrosis in unilateral urinary obstruction (UUO) rats. Also, our study was to confirm eplerenone prevents cardiac fibrosis by inhibiting angiogenesis in unilateral urinary obstruction rats.

Design and method:
We used a 180-day rat model of unilateral ureteral obstruction (UUO) to replicate the CRS model. Using eplerenone, a blocker of mineralocorticoid receptor (MR), to test the effect of aldosterone in cardiac fibrosis induced by UUO. HE staining was performed to observe the pathology of myocardial tissue. The degree of myo-cardial tissue fibrosis was observed by Masson and Sirius red staining. Immunohistochemical staining was applied to detect the expression of CD34 and CD105 in myocardial tissue, and immunofluorescent staining was performed to examine the expression of CD34, COLI/COLIII and alpha-SMA. The expression of signal pathway-related protein VEGFA, VEGFR2, nuclear factor kappa-B and IL-1 beta were tested by western blot. RT-PCR was used to detect the mRNA levels of SGK-1, nuclear factor kappa-B and IL-1beta.

Results:
The results shows that the development of pathological cardiac remodeling and cardiac dysfunction in UUO rats. Moreover, there was more angiogenesis and endothelial-mesenchymal transition (End-MT) in the UUO group, and these effects were inhibited by eplerenone.

Conclusions:
The results indicated that this cardiac fibrosis was associated with angiogenesis and endothelial-mesenchymal transition (End-MT) related to aldosterone and mineralocorticoid receptor (MR) activation. Moreover, in association with the MR/IL-1beta/VEGFA signaling pathway, early treatment with the MR antagonist eplerenone in rats with UUO-induced CKD may significantly attenuate MR activation and cardiac fibrosis.
PS-B04-3: SHORT-TERM LOW IODINE DIET EXACERBATES VASCULAR REACTIVITY WITHOUT ALTERING THYROID HORMONE PROFILES IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Moseki Phillip , Graham Delyth , Salt Ian , Combet Emilie 
Published: January 2023

Objective:
Iodine is an essential microelement required for thyroid hormone (TH) synthesis and regulation. Recent evidence links iodine to direct cardiovascular functional changes independent of TH. We aimed to determine the short-term effect of a low iodine diet on cardiovascular parameters in young Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) rats.

Design and method:
5-week-old WKY and SHRSP males and females (n = 5–7 per group) were assigned a normal (NID) or low iodine (LID) diet for 4 weeks. Iodine content was 1.2 mg/kg for NID and 0.211 mg/kg for LID. Tail cuff blood pressure (BP) and body weight were measured pre-diet and weekly. Transthoracic echocardiography, food intake, water consumption, and urine production were determined pre-diet and fortnightly. At sacrifice, thyroid tissue was weighed and snap-frozen for sodium iodide symporter (NIS) gene expression. Plasma was collected for thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) measurement. Third-order mesenteric arteries were assessed for vascular function using wire myography.

Results:
Baseline TSH, fT3, and fT4 levels were not significantly different between strains. LID did not influence food intake, body weight, thyroid weight, left ventricular (LV) mass, relative wall thickness (RWT) or BP. TSH levels, but not fT3 or fT4, significantly increased by 63.3% in SHRSP males (p = 0.0002) and 74.5% in females fed LID (p = 0.018) but not in WKY when compared to strain, sex- and age-matched rats fed NID. NIS expression significantly increased by 3.27-fold in WKY males fed LID when compared to WKY males fed NID (p = 0.03) but not in SHRSP males. A similar trend in NIS expression was observed in WKY females fed LID. Water intake/urine output ratio significantly increased by 53.62% in SHRSP females fed LID compared to SHRSP females fed NID (p = 0.04). Trends towards reduced stroke volume (SV) and cardiac output (CO) were observed in males fed LID compared to those fed NID irrespective of strain. Vascular reactivity to U46619 in third-order mesenteric resistance arteries was significantly increased by 24.9% in SHRSP males fed LID compared to SHRSP males fed NID (p = 0.03). A similar trend was evident in SHRSP females fed LID when compared to SHRSP females fed NID.

Conclusions:
Our results demonstrate that short-term LID increases vascular reactivity in SHRSP male rats and is associated with altered expression of genes that encode iodine transport proteins yet independent of thyroid hormone levels.
PS-B04-5: AMELIORATIVE POTENTIAL OF COMBINATION OF VITAMIN D AND SILDENAFIL AGAINST MONOCROTALINE-INDUCED PULMONARY HYPERTENSION IN RATS VIA ACTIVATING ENOS
Authors: Yadav Harlokesh Narayan , Shah Sadia 
Published: January 2023

Objective:
The life expectancy in PAH is very less, and only symptomatic treatment is available. Patients with pulmonary hypertension are mostly diagnosed with co-existing vitamin D deficiency. In PAH, there is an increase in the level and expression of PDE 5 enzyme that results in increased degradation of cGMP but there is also a simultaneous decrease in the activation of cGMP due to a subsequent decrease in eNOS mediated nitric oxide synthesis. Thus, limiting the efficacy of sildenafil as monotherapy in the treatment of PAH. Furthermore, vitamin D deficiency is also associated with reduced expression of eNOS mediated NO synthesis, which further decreases cGMP synthesis thus increasing disease severity. Hence, this study was undertaken to study the combined effect of sildenafil and vitamin D therapy in monocrotaline-induced PAH in rats.

Design and method:
Rats were fed on a vitamin D deficient diet with exposure to filtered fluorescent light to induce vitamin D deficiency. PAH was induced by a single s.c. injection of MCT 50 mg/kg. Rats were divided into 6 groups: Control, MCT, MCT+Sildenafil, MCT+Vitamin D, MCT+Vitamin D+Sildenafil and MCT+L-NAME+Vitamin D+Sildenafil. Haemodynamic, echocardiographic, histopathological and biochemical parameters were analysed. The expression and level of eNOS was done using immunohistochemistry and western blot.

Results:
The effect of the vitamin D sildenafil combination group was significantly higher than the vitamin D and sildenafil treated alone groups. This protective effect of vitamin D sildenafil combination in PAH is attenuated when administered with L-NAME (20 mg/kg). Furthermore, the administration of MCT reduced the expression of eNOS, which was significantly reversed by the treatment with vitamin D sildenafil combination compared to vitamin D and sildenafil alone.

Conclusion:
The effect of vitamin D in the treatment of PAH is comparable to sildenafil alone and is further improved when given in combination with sildenafil. Moreover, if pulmonary hypertension is accompanied by vitamin D deficiency it results in increased disease severity of PAH. Thus, sildenafil when combined with vitamin D may exert a synergistic effect in amelioration of symptoms and disease severity in patients of pulmonary hypertension.
PS-B04-8: YM750, AN ACAT1 INHIBITOR, REDUCES ALDOSTERONE SECRETION BY DECREASING ADRENAL CYP11B2 EXPRESSION
Authors: Shimada Hiroki , Otsubo Yuri , Hata Shuko , Sato Ikuko , Yamazaki Yuto , Yokoyama Atsushi , Suagwara Akira , Nakamura Yasuhiro 
Published: January 2023

Primary aldosteronism (PA) is a refractory hypertension that accounts for approximately 5%-10% of hypertensive patients. aldosterone-producing adenomas and idiopathic hyperaldosteronism are known causes of PA. In aldosterone-producing adenomas, depolarization due to somatic mutations of ion channels in adrenocortical cells is considered the cause of aldosterone oversecretion.
Recently, there have been reports on the expression of various cholesterol-metabolizing enzymes in aldosterone-producing adenomas, suggesting that intracellular cholesterol metabolism is very important for aldosterone secretion. We present here the possibility that an inhibitor of Acetyl-CoA acetyltransferase (ACAT1), an enzyme that converts cholesterol to cholesteryl esters, may inhibit aldosterone secretion by depolarization in adrenal cells.
Potassium chloride and YM750, an ACAT1 inhibitor, were added to human adrenocortical carcinoma, H295R cells. Then, we measured aldosterone synthase gene, CYP11B2 mRNA expression level. As a result, the expression level of CYP11B2 decreased. Both NURR1 and NGFIB mRNA expression levels also decreased. Additionally, aldosterone production was also measured and found to be significantly decreased in the YM750 added group. Next, angiotensin II was added and the inhibitory effect of YM750 was examined. The results showed that CYP11B2 expression was not decreased. This indicates that YM750 decreased the induction of CYP11B2 expression in a potassium chloride-induced stimulus-specific manner.
The experimental results suggest that YM750 specifically inhibits CYP11B2 gene expression by cell depolarization and suppresses aldosterone secretion. However, there are few reports of cholesterol metabolism affecting CYP11B2 gene expression. In this study, we found that intracellular cholesterol metabolism may affect CYP11B2 gene expression. We plan to investigate the relationship between ACAT inhibition and CYP11B2 gene expression in detail mechanisms in the future.
PS-B04-11: THE EFFECTS OF PLANT-DERIVED COMPOUNDS AND PLANT EXTRACTS ON BLOOD PRESSURE IN AN AVP INDUCED RAT MODEL OF PRE-ECLAMPSIA
Authors: Reddy Rebecca , Govender Nalini , Baijnath Sooraj , Singh Sanil , Naicker Thajasvarie 
Published: January 2023

Objective:
In resource-limited settings, such as South Africa, hypertensive disorders of pregnancy such as preeclampsia (PE), is the most common direct cause of maternal deaths. Current management of PE includes the use of pharmaceutical drugs, which are frequently associated with major side-effects and not cost effective. Globally, angiotensin-converting enzyme inhibitors (ACEi) are widely used antihypertensive drugs. As a result, patients are reliant on traditional medicine obtained from medicinal plants to manage hypertension related issues. Hence, this study aimed to determine the anti-hypertensive effects of the plant derived bioactive compounds (hesperidin and nicotinamide) and medicinal plant extract (Dombeya rotundifolia ) in a Sprague Dawley rat model induced with arginine vasopressin (AVP).

Methods:
Female Sprague Dawley rats (n = 30; pregnant AVP saline (PAVPS), pregnant AVP hesperidin (PAVPH), pregnant AVP nicotinamide (PAVPN), pregnant AVP Dombeya rotundifolia (PAVPP), and positive control; pregnant AVP captopril (PAVPC) received a continuous dose of AVP (200 ng/h) via subcutaneous mini osmotic pumps for 18 days. Treatment groups were orally dosed with either 200 mg/kg/BW of the bioactive compounds; the plant extract; or 40 mg/kg/BW of captopril over a 2-week period. Blood pressure was recorded throughout gestation and fetal and placental weights were taken following sacrifice.

Results:
Treatment groups (PAVPH, PAVPN and PAVPP) significantly (p < 0.05) reduced diastolic, systolic, and mean arterial blood pressure in AVP treated rats when compared to the control group (PAVPS). Furthermore, urine output differed significantly in the AVP-treated vs the treatment groups (p < 0.05). Moreover, placental, and individual pup weight were significantly different in the PAVPS vs PS and treatment groups (p < 0.05).

Conclusion:
This study showed that Hesperidin, Nicotinamide and Dombeya rotundifolia have the potential to cause a blood pressure lowering effect. Thus, these bioactive compounds and extract may be considered as potential molecules in the development of new naturally occurring pharmaceutical products, as a means to reduce maternal and neonatal mortality and morbidity.
PS-B05-3: CARDIOVASCULAR RESPONSES EVOKED BY LOW ENERGY CONTINUOUS VERSUS INTERMITTENT STIMULATION OF THE AORTIC BARORECEPTOR AFFERENTS IN HYPERTENSION
Authors: Salman Ibrahim M , Ameer Omar Z , McMurray Sheridan , Hassan Sarah F , Sridhar Arun , Lewis Stephen J , Hsieh Yee Hsee 
Published: January 2023

Objectives:
Device-based neurostimulation of the carotid baroreceptors is a novel approach to control hypertension. We have previously demonstrated the significance of aortic baroreceptor afferent nerves as a viable alternative neuromodulation target to carotid baroreceptors in lowering mean arterial pressure (MAP) in hypertension. We have also shown that appreciable reductions in MAP do not necessarily require the use of ultrahigh stimulation parameters. In this study, we aimed to investigate if energy consumption for neuromodulation of aortic baroreceptor afferents could be lowered further by using intermittent as opposed to continuous stimulation.

Design and method:
In male anesthetized spontaneously hypertensive rats (SHRs), the effects of continuous (20 sec) versus intermittent (5 sec ON/3 sec OFF and 5 sec ON/5 sec OFF for 20 sec) stimulation of the left aortic depressor nerve (ADN) on MAP, heart rate (HR), mesenteric (MVR) and femoral (FVR) vascular resistance were assessed using low (5 Hz) and high (15 Hz) frequencies delivered at 0.4 mA and 0.2 ms.

Results:
Continuous and intermittent low frequency stimulation produced similar sustained decreases in MAP, HR, MVR and FVR. Continuous high frequency stimulation produced larger reductions in MAP, HR, MVR and FVR compared with all low frequency and/or intermittent high frequency stimulations.

Conclusions:
Low charge intermittent stimulation of the aortic baroreceptor afferents maintains the required reductions in MAP levels in hypertension and intermittent delivery of the electrical stimulus can further lower energy consumption for neuromodulation. Clinically, these findings may provide useful insight for studies using baroreflex modulation in resistant hypertension and other cardiovascular diseases.