bluuebunny/crossref_metadata_2025_split huggingface dataset:
The “forgotten circulation”: Sympathetic control of mesenteric venous capacity in conscious hypertensive rats
Authors: McBryde Fiona , Emans Tonja , Barrett Carolyn , Paton Julian 
Published: May 2023

The venous circulation is often “forgotten,” as cardiovascular research and therapeutic intervention focusses predominantly on arteries. However, systemic veins store two-thirds of blood volume at rest, with reservoir beds such as the mesenteric circulation receiving dense sympathetic innervation, suggesting a critical neurogenic role for the mobilization of blood. The impact of hypertension on sympathetic regulation of venous circulation remains unclear. We hypothesized that capacity of mesenteric vasculature is impaired in spontaneously hypertensive rats (SHR) and that reducing sympathetic drive will increase mesenteric buffering of excess volume.SHR (n=6) and Wistar rats (n=7) were instrumented with telemeters recording arterial and venous pressures, and an atrial balloon for assessment of mean circulatory filling pressure (MCFP). Arterial (inflow) and venous (outflow) mesenteric flow probes were implanted to measure total mesenteric volume fluctuation. Mesenteric vascular capacity was challenged with 20% volume load of intravenous saline. In SHR sympathetic drive was reduced via hexamethonium (10mg/kg) or via carotid body denervation (CBD).MCFP was elevated in SHR (+2.7±0.5mmHg, p<0.01 vs Wistars). MCFP in SHR was reduced by hexamethonium (-2.6±0.6; p=0.01 vs Baseline, n=5) and CBD (‑2.0±0.7mmHg; p=0.04 vs Baseline, n=5). In normotensives volume load was accommodated by the mesenteric bed, with a net total influx of blood (+5.4±2.2ml; n=7). In contrast, SHR showed a counter-intuitive net efflux of blood from the mesenteric bed (-1.6±1.4ml; p=0.04 vs Wistars, n=6). Preliminary results indicate that hexamethonium and CBD tended to increase the ability of the mesenteric bed to accommodate volume (hexamethonium: +1.9±1.5, n=6; CBD: +0.8±0.6ml, n=3).We show that SHR have higher venous tone and reduced capacity to accommodate excess volume within the mesenteric vascular bed. Reductions in sympathetic drive reduced venous tone and improved the ability to accommodate volume load. Inhibiting sympathetic activity may provide a novel therapeutic opportunity to restore venous mesenteric capacity and potentially ameliorate hypertension. Marsden Fund, Royal Society of New Zealand; Health Research Council of New Zealand This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
The role of Cola nitida on gastric acid secretion and its mechanism of action in male Wistar rats
Authors: Ayegboyin Olusola , Alada AbdulRasak 
Published: May 2023

This study investigated the effect of an aqueous extract of Cola nitida (AECN) and decaffeinated (DECAF) extract of kolanut on gastric acid secretion and its mechanism of action in rats. Previous reporters only speculated that the biological effect of kolanut in causing gastric acid secretion could be ascribed to its caffeine content, also the mechanism is not fully elucidated. In addition, none of the previous reporters has investigated the effect of decaffeinated kolanut extract on gastric acid secretion. Sixty (60) male adult Wistar rats divided into twelve groups of five rats each were used for this study. Groups 1 and 2 received normal saline orally and intravenously respectively at a dose of (1 ml/kg), 3 and 4 received 25 mg/kg of (AECN) orally and intravenously respectively, group 5 received (100mg/kg) AECN orally, groups 6 and 7 received 25mg/kg of (DECAF) both orally and intravenously respectively, group 8 received 100mg/kg of DECAF orally, groups 9 and 10 were pre-treated with cimetidine 12 μmoles/kg intravenously followed by 25 mg/kg AECN and DECAF respectively, groups 11 and 12 were pre-treated with i.v atropine (0.2 mg/kg) followed by 25 mg/kg of AECN and DECAF respectively. Gastric acid secretion was determined by continuous perfusion of rats' stomachs under urethane anesthesia. Data collected were expressed as mean ± SEM. Statistical significance at P≤0.05 was determined using Student’s t-test analysis. The oral administration of AECN (25mg/kg and 100mg/kg) and i.v AECN (25mg/kg) caused a significant increase (P≤0.05) in gastric acid secretion (GAS) with pronounced effect than DECAF group. The oral administration of 25mg/kg and 100mg/kg of DECAF and intravenous administration of (25mg/kg) DECAF caused a significant increase in gastric acid secretion. The administration of cimetidine and atropine significantly reduced gastric acid secretion. In conclusion, aqueous extract of Cola nitida and decaffeinated kolanut extract exert significant gastric acid secretion in this study. Also, the mechanisms exhibited by kolanut in stimulating gastric acid secretion in this study could be attributed to stimulating both the histaminergic H2 and cholinergic (Muscarinic M3) receptors since cimetidine and atropine blocked/reduced its effect. This research work was self-funded. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Intestinal inflammation caused by anti-cancer drugs is ameliorated by ginsenoside
Authors: Tsujii Taisei , Kato Daisuke , Jonan Shizuka , Amagase Kikuko 
Published: May 2023

Background & Aim: It has been reported that 5-fluorouracil (5-FU), a widely used anticancer drug, causes intestinal inflammation due to shortening of small intestinal villi and destruction of the glandular fossa, resulting in diarrhea and weight loss. Although Ginsenoside Rd (GRd) and Ginsenoside Re (GRe) are saponins found in carrots and have been reported to have anti-inflammatory effects on the gastrointestinal tract, these compounds have not been reported to have anti-inflammatory effects on the small intestinal mucositis induced by 5-FU. In the present study, we investigated the effects of GRd and GRe on the 5-FU-induced mucoenteritis. Materials & Methods: Male C57BL/6N mice (20-25 g) were treated with 5-FU (50 mg/kg i.p.) and GRd (60 or 100 mg/kg p.o.) or GRe (100 mg/kg p.o.) once daily for 7~8 days. 5-FU was dissolved in saline and GRd and GRe were dissolved in 0.5 % CMC. The group receiving saline and 0.5% CMC was designated as the Vehicle group. Body weight and degree of diarrhea (score 0: normal stools, 1: soft stools, 2: severe soft stools, 3: diarrhea, 4: severe diarrhea) were measured daily during the treatment period. The degree of intestinal inflammation was evaluated by histopathological examination using hematoxylin/eosin (H&E) staining, measurement of myeloperoxidase (MPO) activity, and mRNA expression of inflammation-related molecules after the end of drug administration. The expression of NF-κB in the small intestine was examined by immunohistochemical staining. Results: Decreased body weight and exacerbation of diarrhea were observed from the third day of 5-FU administration, and combined administration of GRd or GRe had no effect on these symptoms. Histopathological observations showed that 5-FU administration shortened small intestinal villi and reduced the number of small intestinal crypt, compared to the vehicle group. However, co-administration of GRd and GRe, significantly suppressed the decrease in the number of small intestinal crypts and cells in the crypt by 5-FU treatment and tended to suppress the increase in expression of TNF-α mRNA. MPO activity in the small intestinal mucosa were increased by 5-FU treatment, and the increase was clearly suppressed in the GRd or GRe combination treatment groups. In addition, the expression of NF-κB was clearly increased at 24 hours after the last dose of 5-FU compared with the Vehicle group, and the increase of NF-κB expression by 5-FU administration was clearly suppressed by the concomitant use of GRd. Conclusion: The results obtained in this study suggest that GRd and GRe show anti-inflammatory effect against 5-FU-induced enteritis and that NF-κB is involved in their action. The authors declare no conflict of interest. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Kv7 channel dysfunction is involved in hyperactivity of posterior insular cortex neurons in hypertension
Authors: Sheng Zhaofu , Sheng Zhaofu , Zheng Peiru , Li De-Pei 
Published: May 2023

Elevated sympathetic outflow is a key component of pathogenesis of hypertension. However, the source driving increased sympathetic vasomotor tone remain unclear. The posterior insular cortex (PIC) is a brain region involved in regulating blood pressure and sympathetic tone. Neurons in the PIC project to the rostral ventrolateral medulla (RVLM). Neuronal Kv7 channels play a vital role in controlling the excitability of neurons. This study determined the role of Kv7 channels in regulating RVLM-projecting PIC neurons in spontaneously hypertensive rats (SHRs). Kv7.2, Kv7.3, and Kv7.5 subunits expression level were compared between Wistar-Kyoto (WKY) rats and SHRs. Whole-cell recording was used to compare the firing activity and M-current in RVLM-projecting PIC neurons retrogradely labelled by Fluospheres injected into the RVLM. We found that the protein expression levels of Kv7.3 and Kv7.5 in the PIC were significantly lower in SHRs than in WKY rats, while Kv7.2 levels did not differ between WKY and SHRs. Immunofluorescent staining reviewed that Kv7.2, Kv7.3, and Kv7.5 subunits were expressed on retrogradely labeled RVLM-projecting PIC neurons. Electrophysiological recording results showed that the basal firing activity of labeled PIC-RVLM projection neurons was significantly greater in SHRs than in WKY rats. Blocking M-currents with XE-991 increased both spontaneous and depolarization-triggered firing rate of RVLM projecting PIC neurons in WKY rats, whereas XE-991 did not alter either spontaneous or depolarization-triggered firing rate of these neurons in SHRs. These data suggest that hyperactivity of RVLM projecting PIC neurons in SHRs is attributed to reduction of Kv7 channel expression and activity. Our findings revealed a novel mechanism underlying elevated sympathetic vasomotor activity in hypertension. National Heart, Lung, and Blood Institute grant HL142133 and HL139523, and HL159157 to D-P. L. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Endothelial function of vascular segments that comprise a murine arteriovenous fistula
Authors: Mookherjee Sohom , Hill Nathan , Fairbourn Brayden , He Yuxia , Boudina Sihem , Shiu Yan-Ting , Lee Timmy , Symons John David 
Published: May 2023

Approximately 60% of arteriovenous fistulas (AVFs) created in hemodialysis patients in the United States fail to mature. Understanding the underlying pathobiology is requisite to design and implement new treatments. Mechanisms responsible for AVF failure include intimal hyperplasia and poor lumen expansion. Compromised vasoreactivity also might play a role. Our murine AVF model comprises the external jugular vein (EJV) connected to the carotid artery (CA), establishing 3 component parts to the AVF, i.e., proximal CA, EJV, and distal CA. Upon AVF creation, the EJV is acutely exposed to higher pressures and disturbed flow, known causes of endothelial cell dysfunction. First, we tested the hypothesis that endothelial function is impaired in EJVs (193 ± 27 μm i.d.) from AVF mice (i.e., EJV-AVF; n= 5 males and 5 females) vs. EJVs (228 ± 18 μm i.d.) from naïve animals (EJV-Con; n=6 males and 4 females). Three days after creating the AVF, using isometric tension procedures, dose-dependent vasocontraction to the Thromboxane A2 (TxA2) receptor agonist U46619 was robust in the EJV-Con (p<0.05) but was absent in the EJV-AVF segment. Because vasocontraction is necessary to subsequently test endothelium-dependent vasorelaxation, our hypothesis could not be evaluated. Our second hypothesis was that endothelial function is impaired in the distal (185 ± 7 μm i.d.) vs. proximal (230 ± 10 μm i.d.) CA, secondary to disturbed flow patterns. U46619 -evoked vasocontraction was greater (p<0.05) in the proximal vs. distal CA segment of the AVF. Acetylcholine-evoked vasorelaxation was greater (p<0.05) in distal vs. proximal CA, whereas responses to sodium nitroprusside were similar between groups. These findings do not support our hypothesis and suggest that endothelial function is better in the distal vs. proximal CA of the AVF, whereas vascular smooth muscle function is similar between segments. Ongoing studies are evaluating endothelial function in each segment of the AVF 21-days after creation. Supported by R01HL153244 NIH/NIDDK (TL, YTS, JDS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Uncovering the relationship between optic atrophy-1 protein and mitochondria function
Authors: Chapa Xavier , Garcia Jorge , Bazil Jason , Javadov Sabzali 
Published: May 2023

Mitochondria, known as the powerhouse of the cell, also participate in the regulation of ion homeostasis, redox status, cell growth and differentiation, lipid metabolism, and cell death. The inner mitochondrial membrane (IMM) plays a crucial role in the regulation of mitochondrial metabolism and function. The dynamin-related GTPase optic atrophy-1 (OPA1) localized in the IMM is responsible for mitochondria fusion. In addition, OPA1 has been shown to play an important role in maintaining the structural integrity and functional activity of mitochondrial cristae. We have recently shown that mitochondrial swelling stimulates enzymatic cleavage of OPA1 by OMA1, a zinc metallopeptidase, which converts long-OPA1 (L-OPA1) to short-OPA1 (S-OPA1). Cleavage of L-OPA1 was suggested to diminish mitochondrial fusion and bioenergetics leading to cell death. The role of OPA1 cleavage and OMA1 activation under diverse swelling conditions has not yet been elucidated. In this study, we investigated the role of OPA1 cleavage under various mitochondrial swelling conditions in the presence and absence of Myls22 (an OPA1 inhibitor), and TPEN (a zinc-chelator and OMA1 inhibitor). Cardiac mitochondria were isolated from Sprague Dawley rats and their function was assessed under Ca2+-induced mitochondrial swelling with oxoglutarate and malate (OM) with/without ADP. Our dose-dependent experiments revealed that Myls22 and TPEN exert the maximum effect at 50 and 5 μM, respectively. Next, we found that the maximum respiration rate (state 3) of mitochondria for complex I is diminished by both inhibitors. However, neither Myls22 nor TPEN prevented alterations in mitochondrial respiration rates, swelling, membrane potential, and calcium retention capacity induced by Ca2+. Finally, we evaluated the protein expression of L-OPA1 via western blot and found more OPA1 cleavage under state 3 compared to state 2 respiration rate suggesting the regulatory role of S-OPA1 in mitochondrial respiration. Thus, our data demonstrate that although mitochondrial swelling stimulates L-OPA cleavage associated with mitochondrial dysfunction, inhibition of OPA1 cleavage/OMA1 activity by Mysl22/TPEN is ineffective in ameliorating the effects of Ca2+-induced mitochondria swelling. This study was supported by the National Science Foundation (Grant 2006477). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
17-B estradiol ameliorates oxidative stress, inflammation and apoptosis in the heart and aorta of ovariectomized Sprague Dawley rat model of collagen induced rheumatoid arthritis (CIA)
Authors: Shahzad Huma 
Published: May 2023

Menopause and rheumatoid arthritis (RA) are both known to cause elevation of blood Pressure in women, and it is known that RA is more prevalent in women around menopausal age. However, the mechanism of elevated blood pressure in postmenopausal RA women is not known. Thus, the aim of this study was to identify the underlying mechanisms of increased blood pressure in postmenopausal RA women by using ovariectomised RA rat models. Ratswere randomly divided into six groups: sham, ovariectomised (Ovx), RA induced ovariectomised (Ovx+RA), and RA induced ovariectomised plus 17 β-oestradiol, baricitinib orlosartan. Blood pressure was measured through carotid artery cannulation. Haematoxylin andEosin (H&E) and Picro Sirius Red staining was performed on the aorta and heart tissues toevaluate histological alterations and collagen deposition. Immunohistochemistry, immunofluorescence and qPCR methods were used to evaluate the oxidative, inflammatory, growth and fibrosis, and apoptosis markers in the aorta and heart tissues. Mean arterial pressure(MAP) was significantly raised in the Ovx rats compared to sham rats and slightly raised without significant difference in the Ovx+RA rats compared to Ovx rats. MAP in the RA induced ovariectomised rats were significantly reduced with 17 β-oestradiol and losartantreatment. H&E and Picro Sirius staining revealed enhanced collagen deposition in the aortaand heart tissues and increased fibrosis in the heart tissue of the Ovx+RA rats. The collagen deposition and fibrosis were reduced with 17 β-oestradiol treatment. Immunohistochemistry, immunofluorescence and qPCR studies revealed that Ovx+RA rats had elevated expression of oxidative markers such as endothelial nitric oxide synthase (eNOS), inducible nitric oxidesynthase (iNOS), NADPH oxidase 2 (Nox2) and NADPH oxidase 4 (Nox4), inflammatory markers such as toll-like receptor 4 (TLR4) and nuclear factor kappa-light-chain-enhancer ofactivated B cells (NF-ĸB), growth and fibrosis marker such as vascular endothelial growth factor (VEGF), and apoptosis marker such as caspase-3 in the aorta and heart tissues. The expressions of these markers were reduced with 17 β-oestradiol treatment. In conclusion, hypertension in postmenopausal RA women occurs due to enhanced oxidative stress, inflammation, fibrosis, and apoptosis; oestrogen treatment reduces the blood pressure inpostmenopausal RA women by inhibiting these mechanisms. The research work is supported by Fundamental research grant scheme 2020, Ministry of Higher education, Malaysia. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Developing a multiscale mathematical model of protein uptake along the mouse proximal tubule
Authors: Shipman Katherine , Baty Catherine , Edwards Aurelie , Weisz Ora 
Published: May 2023

The proximal tubule (PT) efficiently reclaims albumin and other proteins that escape the glomerular filtration barrier to maintain a protein free urine. The recovery of filtered proteins occurs via receptor-mediated endocytosis facilitated by the multiligand receptors megalin and cubilin. PT health is impacted by excess albumin uptake that occurs when the glomerular barrier is breached and by nephrotoxic drugs that enter cells in a megalin/cubilin dependent manner. Understanding where and how endocytic uptake occurs along the PT axis is key to predicting disease outcomes and to devising strategies to protect PT cells from nephrotoxic insults. Transcriptomic and proteomic studies in male rodents have demonstrated a difference in the expression of megalin and cubilin across the S1, S2, and S3 sub-segments that comprise the PT. Based on these differences in expression, we previously developed an axial model of protein uptake in mice which predicts that most uptake under normal conditions occurs in the S1 segment, with later PT segments providing excess uptake capacity under nephrotic conditions. Separately, we created a kinetic model that predicts rates of megalin trafficking rates in S1 segment cells. This model demonstrated that both the actual level and the fraction of total receptor present at the apical surface are critical determinants of endocytic capacity. To integrate our cell-based kinetic model of megalin traffic into the axial model, we used imaging-based approaches to quantify the expression and distribution of megalin and cubilin in SGLT2-positive S1 and SGLT2-negative S2 segments in fixed cortical kidney sections from wild-type C57BL/6 age-matched male and female mice. The fraction of megalin and cubilin at the apical surface was determined by colocalization with the brush border marker, villin, in regions where AP2, a marker for endocytic vesicles, was excluded. These data will be incorporated into our current axial model to develop a multiscale model of protein uptake along the length of the PT. The expanded model will improve our understanding of how endocytic capacity along the PT in vivo is regulated under normal and disease conditions and allow us to determine whether there are sex-based differences in the recovery of filtered proteins. National Institutes of Health T32 DK007052, F31 DK121394, R01 DK125049, R01 DK118726 and ASN Foundation for Kidney Research Pre-Doctoral Fellowship Award This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.