bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Dietary Salt on Blood Pressure Variability, Cerebral Perfusion and Cognitive Function in Young-Adult Male Rats
Authors: Sun Fen , Zhao Lu-Ping , Zhang Jin-Yang , Jin Chao , Jin Qi 
Published: May 2023

Background: There is controversy about the relationship between dietary salt intake and cognitive function. Experimental studies showed that extremely high salt diets increased blood pressure (BP) levels, leading to cognitive impairment. However, extremely high salt diets are not clinically relevant. The present study examined how high dietary salt could affect cognitive function and whether these effects are via BP stability and cerebral hypoperfusion. Methods: SD rats (male, young adult) were on the control diet (0.4% NaCl), low salt diet (0.1% NaCl), or high salt diets (with three does at 1%, 2%, or 4% NaCl) for 12 weeks. BP levels, heart rate (HR), and BP variability (SD and CV) were measured repeatedly at baseline, 1, 2, 3, 4, 6, 8, and 12 weeks after the onset of the diet. Anxiety and cognitive function (open field, novel object recognition, and T-maze) were measured repeatedly at baseline, 4, 8, and 12 weeks after the onset of the diet. Blood Na+ and cerebral blood flow (CBF) were measured at the endpoint. Results: Rats with the low salt diet showed significantly reduced systolic BP (SBP) and diastolic BP (DBP) levels compared to those with the control diet and high salt diets at 8 weeks after the onset of the diet. Notably, rats with the low salt diet had the highest SBP variability (SBPV) and DBPV, while those with the control diet showed the lowest SBPV and DBPV. In high salt diet groups, SBPV and DBPV increased in a dose-dependent manner. There is no significant difference in HR between groups. Rats only with a 4% NaCl diet showed worse cognitive function compared to rats with low salt and control diet 8 weeks after the onset. Blood Na+ was similar between groups. Interestingly, the high salt diet increased the CBF in a dose-dependent manner. The CBF of the low salt diet was similar to those with 2% salt die, and the CBF of the control group was the lowest. Conclusions: This study suggests that a moderate-high salt diet would not affect cognitive function in young-adult male SD rats. Only consumption of an extremely high salt diet impaired cognitive function, and this harmful effect was not via cerebral hypoperfusion. Moreover, both low and high salt diets increased BPV. This research was funded by the START-UP FUNDING OF HANGZHOU NORMAL UNIVERSITY, grant number 4255C50221204123 (Dr. Fen Sun). 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.
Myoglobin-driven ET-1 production and downstream activation of TRPC3- but not TRPC6-dependent vasoconstriction contributes to rhabdomyolysis-induced AKI
Authors: Afolabi Jeremiah , Kanthakumar Praghalathan , Williams Jada , Kumar Ravi , Adebiyi Adebowale 
Published: May 2023

Acute kidney injury (AKI) is the most severe and life-threatening complication of rhabdomyolysis, with 10-40% of patients developing some form of kidney insufficiency within days. Experimental evidence indicates that renal vasoconstriction plays a significant role in the pathophysiology of rhabdomyolysis-induced AKI. Rodents subjected to glycerol-induced rhabdomyolysis exhibited increased plasma concentrations of endothelin-1 (ET-1). Treating glomerular mesangial cells with myoglobin has also been shown to increase the cellular production of ET-1. The downstream effectors of ET-1-induced vasoconstriction are smooth muscle Ca2+ permeable transient receptor potential canonical (TRPC) channels. There are seven members of the TRPC gene family (TRPC1-7). Whereas TRPC2 and 7 are absent, TRPC1, 3, 4, 5, and 6 are expressed in renal vessels, with TRPC3 predominant. TRPC3, TRPC6, and TRPC7 are highly homologous. Although the ET system is known to be associated with rhabdomyolysis-induced AKI, the function of renal vascular ion channels in the disease is unclear. Here, we investigated the involvement of TRPC3 and TRPC6 in glycerol-induced rhabdomyolysis in rats. ET-1 production is increased in myoglobin-treated epithelial cells, the primary source of renal ET. Rhabdomyolysis also increased renal ET-1 production, decreased renal blood flow (RBF), and increased renal vascular resistance, effects attenuated by ET receptor and TRPC channel blocker Pyr3. Furthermore, we used TRPC3 and TRPC6 knockout (KO) rats to support the pharmacological approaches. Basal day and night arterial pressure, heart rate, GFR, plasma creatinine, and BUN were unchanged in WT vs. KO rats. Twenty-four h rhabdomyolysis led to comparable increases in urinary ET-1 production in WT and KO rats. However, rhabdomyolysis-induced decreases in GFR, elevations in BUN, and plasma creatinine were all attenuated in the TRPC3 but not TRPC6 KO rats. Similarly, morphological kidney damage (tubular necrosis, casts, and dilatation) was mitigated in the TRPC3 KO with no protection offered by the KO of TRPC6 channels. Together, our data suggest that myoglobin-driven ET-1 production and downstream activation of TRPC3- but not TRPC6-dependent vasoconstriction contributes to rhabdomyolysis-induced AKI. American Heart Association Predoctoral Fellowship 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.
Gravid grasshoppers produce more energy but jump shorter distances
Authors: Truini Dana , Kirkton Scott 
Published: May 2023

The negative effects of gravidity on locomotion have been well documented in terrestrial vertebrates but are relatively unknown in insects. During gravidity, the egg mass of Schistocerca americana grasshoppers can be up to 40% of their body mass. However, jumping muscle mass remains relatively unchanged during gravidity. Using female grasshoppers that ranged in body size from 1.6 g to 3.3 g (n=25), we investigated how gravidity affects maximal jump performance. Each grasshopper’s maximal jump was captured using eight Qualisys infrared high-speed cameras filming at 1121 fps. Biomechanical data were generated using Qualisys Track Manager and the effects of body size/gravity were analyzed using regression in JMP. Larger grasshoppers have significantly more eggs, a larger egg mass, and a greater portion of their body dedicated to eggs (egg mass: y=0.52x-0.82; r2=0.76; p<0.0001). We found that the take off angle, take off acceleration, force, and time spent in the air during a jump was similar regardless of body size or gravidity. However, larger, more gravid grasshoppers had significantly lower take off velocities (y=-0.40x+4.36; r2=0.22; p<0.02) and did not jump as far (y=-0.18x+1.44; r2=0.18; p<0.05). When we compared the actual jump distance to the predicted jump range, we found that more gravid grasshoppers were significantly closer to the expected range than smaller, less gravid grasshoppers (y=6.23x+77.31; r2=0.16; p<0.05). In addition, more gravid grasshoppers produced significantly more energy during a jump than less gravid animals (y=2.94x+5.77; r2=0.19; p<0.05). The increased jump energy of more gravid grasshoppers may be due to an increased reliance on anaerobic ATP production. This supports previous work that gravid grasshoppers have more problems with oxygen delivery. For example, gravidity reduces the total tracheal respiratory volume by 10%, reduces tidal volumes, and increases respiratory rates. Future work will measure phospho-arginine and lactate to determine, if due to oxygen delivery problems, gravid grasshoppers rely more on anaerobic ATP to produce powerful escape jumps. This research was supported by the National Science Foundation (Award 1827495 to SDK) and Union College Biology Department. 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.
Angiotensin-(1-7) improves blood pressure and cardiovascular autonomic function in human aging
Authors: Miller Amanda , Arnold Amy 
Published: May 2023

Background: Aging is the largest independent risk factor for developing hypertension and cardiovascular disease (CVD); however, the molecular mechanisms underlying age-related CVD remain poorly understood. Our laboratory recent published that levels of angiotensin (Ang)-(1-7), a protective hormone of the renin-angiotensin system, are reduced in healthy aged mice and that chronic restoration of Ang-(1-7) levels lowers blood pressure and sympathetic tone in aged mice. In this translational study, we hypothesized that, aging in humans is associated with low Ang-(1-7) and that restoring levels of Ang-(1-7) can decrease blood pressure via modulation of the autonomic nervous system. Methods: To test this hypothesis, plasma Ang-(1-7) levels and blood pressure were measured in older (>60 yrs n=8) and younger (<40 yrs, n=10) healthy humans. In a separate double-blind, randomized, crossover study, we performed acute intravenous (IV) infusion of Ang-(1-7) and saline in older adults (n=3). Ang-(1-7) was infused at escalating doses (2ng/kg, 6ng/kg, 8ng/kg; 10 minutes per dose), with the highest dose held for an additional 70 minutes. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were measured continuously before and during Ang-(1-7) and saline treatments. Heart rate variability (HRV) and low frequency systolic blood pressure variability (LFSBP) were calculated via spectral analysis methods. Results: Plasma Ang-(1-7) levels were lower in older versus younger adults (9.4±1.5 vs. 28.0±4.9 pg/mL, respectively; p = 0.005), with no differences in plasma Ang II levels. Ang-(1-7) was inversely correlated to systolic blood pressure in older adults (r2=0.497, p=0.034), but not in younger adults (r2=0.110, p=0.384). In older adults, acute IV Ang-(1-7) infusion lowered blood pressure [Δ from baseline: -12±10 Ang-(1-7) vs. 4±2 mmHg saline, p < 0.050]. This depressor effect of Ang-(1-7) was associated with decreased measures of sympathetic tone [LFSBP (Δ from baseline: 0.35±0.08 Ang-(1-7) vs. 1.94±0.79 mmHg2 saline; p=0.0372) and MSNA burst incidence (Δ from baseline: -9 Ang-(1-7) vs. 8 A.U. saline)] as well as increased vagal tone (high frequency HRV, Δ from baseline: 295±117 Ang-(1-7) vs. 7±96 s2 saline, p = 0.050). Conclusions: These findings suggest that Ang-(1-7) is lower in healthy aged humans and associated with systolic hypertension. Additionally, acute infusion of Ang-(1-7) decreases blood pressure and sympathetic tone and increase vagal tone in this population. Overall, these data provide further rationale for targeting Ang-(1-7) to improve cardiovascular autonomic control in aging. NIH: K99HL159272, American Heart Association: 18POST33960087 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.
Regulation of endothelial cell mitochondrial phenotype by mechanosensitive ion channel TRPV4
Authors: Dalal Kesha , Katari Venkatesh , Paruchuri Sailaja , Thodeti Charles 
Published: May 2023

Transient receptor potential vanilloid type 4 (TRPV4) is a mechanosensor that regulates endothelial cell (EC) proliferation, migration, and angiogenesis. However, the molecular mechanisms by which TRPV4 regulates EC functions are not well understood. In this study, we investigated if TRPV4 regulates EC function via modulation of mitochondria by employing three types of EC expressing different levels of TRPV4, normal (NEC), TRPV4-deficienct (TEC), and TRPV4 knockout (KOEC). First, we confirmed the functional expression of TRPV4 in these EC using qPCR and calcium imaging. Confocal images upon MitoTracker staining revealed spherical and/or round shaped mitochondria with a perinuclear localization in NEC while in TEC and KOEC the mitochondrial network was elongated and rod shaped with a whole cell distribution. Furthermore, Transmission Electron Microscopy confirmed the presence of clear round mitochondria in NEC compared to elongated mitochondria with distinct cristae in TEC and KOEC. These results indicate increased fusion in TRPV4 deficiency or deletion. When cultured on ECM gels of varying stiffness that mimic stiffness of matrix in pathophysiological conditions such as tumor or heart failure (0.2, 8, and 50 kPa), we found increased distribution of mitochondria in EC with increasing stiffness. Moreover, western blot analysis showed increased expression of a fusion/fission protein ratio (Optic Atrophy 1 (OPA1)/mitochondrial fission factor (MFF)), in TEC and KOEC. Further, uncoupling mitochondrial function by mitochondrial stressors (Oligomycin, FCCP, and Rot/AA) significantly increased basal oxygen consumption rate (OCR), maximal OCR, ATP-linked OCR, and spare capacity in TEC and KOEC than NEC. Finally, a small molecule inhibitor of OPA1, MYLS22, attenuated/normalized the mitochondrial energy metabolism to that of NEC but did not affect NEC. These findings suggest that mechanosensitive TRPV4 channels regulate EC mitochondrial morphology and function through increased OPA1. National Institutes of Health (R15CA202847, R01HL119705, and R01HL148585) to CKT 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.
Sex-specific and immune-cell-specific contributions of beta2 integrins in myocardial ischemia-reperfusion injury
Authors: Fan Zhichao , Liu Wei , Cronin Chunxia , Wen Lai , Ley Klaus , Liang Bruce 
Published: May 2023

Leukocyte recruitment and their mediated inflammatory responses are critical for cardiovascular diseases, including myocardial ischemia-reperfusion (I/R) injury, which accounts for 9% mortality and 10% morbidity rates in ischemic heart disease patients. Blocking leukocyte recruitment in mouse knockouts (KO) of beta2 integrin (CD18) or blocking beta2 integrin with anitibodies in multiple animals significantly reduced infarct size after myocardial I/R injury. However, the cell-specific contribution of leukocyte beta2 integrin to I/R injury is unknown. In this study, we used the newly established CD18flox/flox (hITGB2 KI) mouse strain to address this knowledge gap. We crossed them to CSF1R-cre (CD115) and MRP8-cre (S100A8) and tested the KO of beta2 integrins in different leukocyte populations. Interestingly, CSF1R-cre CD18flox/flox unexpectedly deleted beta2 integrins in all peripheral blood leukocyte populations, including blood neutrophils, monocytes, CD4 T cells, CD8 T cells, B cells, and NK cells. It also elevated the cell number of these leukocyte populations in peripheral blood. In MRP8-cre CD18flox/flox mice, beta2 integrins were only knocked out in neutrophils but not other peripheral blood leukocytes. And only neutrophil number was elevated in peripheral blood. After 35 minutes of myocardial ischemia and 24 hours of reperfusion, we found both CSF1R-cre CD18flox/flox and MRP8-cre CD18flox/flox mice have significantly reduced infarct size compared to cre- controls. However, if we distinguish the sex in analysis, we only found a significant alleviation in female but not male CSF1R-cre CD18flox/flox mice. In contrast, we observed a significant alleviation only in male but not female MRP8-cre CD18flox/flox mice. These results suggested sex-specific and immune-cell-specific contributions of beta2 integrins in myocardial ischemia-reperfusion injury and provided new insights into beta2 integrin targeting therapies. This research was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute, USA (R01HL145454, R41HL156322, and R44HL152710) and a startup fund from UConn Health. 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.
Nitric oxide-mediated vasodilation in tibial bone in young healthy individuals
Authors: Draghici Adina , Ely Matthew , Taylor J. Andrew 
Published: May 2023

Despite the critical importance of sufficient and well-regulated blood flow supply for bone health, regulation of bone blood flow in humans remains poorly understood. We have recently shown that sympathetic and myogenic control have active roles in regulating blood flow to tibial bone in humans. Responses are smaller and delayed in the tibia compared to the whole leg, underscoring the importance of directly interrogating mechanisms underlying bone blood flow control. Nitric oxide (NO) mediated vasodilation is another important regulatory mechanism and studies to date have been confined to assessment of whole limb blood flow responses that primarily reflect muscle. In young healthy individuals (N=8), we characterized NO-mediated vasodilation in tibial blood flow and contrasted it to whole leg blood flow. We employed sublingual nitroglycerin (0.4 mg) as an NO donor. We obtained a 5 min resting baseline, followed by the responses to sublingual nitroglycerin for 10 min in supine subjects. Tibial blood flow was measured continuously via near infrared spectroscopy as total hemoglobin (Hb) and whole leg blood flow as popliteal Doppler flow velocity in the same leg. NO-mediated vasodilation was characterized by peak response, time to peak response, and time to return to baseline over the 10 min response. Tibial blood flow (total Hb) increased rapidly in response to nitroglycerin reaching a maximum of 1.61 ± 0.69 μM after 3.5 min. Afterwards, total Hb steadily declined, returning to baseline values by 10 min. Whole leg blood flow increased at a slower rate reaching a maximum of 7.12 ± 2.72 cm/s after 4.5 min. However, whole leg blood flow remained elevated throughout the entire 10 min measurement. Our results indicate that similar to other vascular beds, bone vasculature has a robust NO-mediated vasodilation, but appears to be faster and shorter lasting compared to the whole leg vasculature. This is not dissimilar from our previous findings indicating different time characteristic time-courses of response to other vascular controllers in tibial bone compared with whole leg vasculature. Paralyzed Veterans of America Research Foundation (AED), NIH NIAMS R21 AR074054 (JAT) 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.
Elucidating the role of renal olfactory receptor 1393 in female Type 1 diabetic mice
Authors: Shaw Britney , Jordan Ali , Shepard Blythe 
Published: May 2023

Diabetes mellitus is a condition arising from the inability to sufficiently produce or respond to insulin, thus manifesting glucose intolerance. We previously identified an olfactory receptor (Olfr1393), which is localized in the renal proximal tubule where glucose is reabsorbed by Sglt1 and Sglt2. Inhibition of these transporters have therapeutic value by decreasing glucose reabsorption and promoting glycosuria to enable improved glucose homeostasis in patients with diabetes. On a normal chow diet, whole-animal Olfr1393 knockout (KO) mice are euglycemic yet present with glycosuria and improved glucose tolerance (Shepard et al 2016). While this phenotype was observed in both male and female mice, the female KOs presented with more robust glycosuria (p=0.03) and a significant reduction in SGLT1 total cellular membrane expression (p=0.04). Recently, we found that when administered low-dose models of Streptozotocin (STZ)—an alkylating agent that depletes pancreatic β cells thereby mimicking Type 1 diabetes—male Olfr1393 KO mice exhibit an improved diabetic phenotype. However, in keeping with other published reports, we found that the wildtype (WT) and KO female mice were unaffected by STZ treatment. This resistance to STZ has been explained by the anti-apoptotic activity of estrogen receptor signaling that protects pancreatic beta islet cells from chemical-induced damage. To overcome this, slow-release pellets containing 4-hydroxytamoxifen (4OH)—an estrogen receptor modulator in pancreatic beta islet cells—were implanted in both male and female C57BL/6J mice three days prior to STZ challenge (55 mg/kg body weight for 5 consecutive days). Using this method, we were able to successfully induce diabetes in the female mice (female fasting blood glucose - 4OH vehicle: 178 ± 3.50 mg/dL; placebo STZ: 330 ± 8.22 mg/dL; 4OH STZ: 436 ± 4.65 mg/dL). We also noted that 4OH-treated male mice exhibited a more robust diabetic phenotype (male fasting blood glucose - 4OH vehicle: 185 ± 4.95 mg/dL; placebo STZ: 450 ± 11.6 mg/dl; 4OH STZ: 575 ± 4.95 mg/dl). With the successful induction of diabetes in female mice, we have used the same method to test the hypothesis that Olfr1393 female KO mice are protected from the development of diabetes and kidney damage. Female Olfr1393 WT and KO mice were administered 4OH pellet implantations followed by STZ-treatment. Preliminary data suggests that loss of Olfr1393 does indeed attenuate, but does not eliminate, the development of hyperglycemia (2-hour fasting blood glucose values - female WT: 368 mg/dL; female KO: 247.5 mg/dL). Future study will determine if the loss of Olfr1393 also protects against diabetes-induced glomerular hyperfiltration and altered renal blood flow. NIDDK, Yale O'Brien Center 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.