bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiofrequency renal nerve ablation decreases blood pressure in SHR accompanied by increased urinary sodium excretion (857.4)
Authors: Gao Juan , Smart Frank , Katsurada Akemi , Navar Gabriel , Kapusta Daniel 
Published: June 2021

We have shown that radiofrequency catheter ablation of the renal arteries (RF‐RDN) decreases blood pressure (BP) in spontaneously hypertensive rats (SHR). Here, we studied the effects of RF‐RDN on changes in water and sodium excretion and urinary angiotensinogen levels in SHR with established hypertension. Methods Nineteen‐week old male SHR were instrumented with telemetry probes for measurement of BP. After 1‐week, control BP was measured. The next day SHR randomly received either bilateral Sham‐RDN (n=5) or RF‐RDN (n=6) of the renal arteries (Biosense Webster Stockert 70 generator and RF‐probe). BP (Systolic, SBP; Diastolic, DBP) was then measured for 2 weeks. Rats were then placed in metabolic cages for collection of urine and measurement of 24‐hr water and sodium balance. Results BP was significantly decreased in RF‐RDN SHR (2 weeks; ΔSBP, ‐12±5; ΔDBP, ‐9±4 mmHg) as compared to sham SHR (2 weeks; ΔSBP, ‐2±2; ΔDBP, 2±2 mmHg). RF‐RDN SHR increased urinary sodium excretion (RF‐RDN, 0.33±0.02; Sham, 0.25±0.03 mEq/day) and food intake (RF‐RDN 21±1; Sham 17±1 g/day). However, there were no significant differences between groups in 24‐hr daily water (RF‐RDN, 21±1; Sham, 19±2 ml) or sodium balance (RF‐RDN, 0.59±0.04; Sham, 0.48±0.06 mEq), or urinary angiotensinogen, protein and creatinine excretion rates. At the end of week 2, kidney norepinephrine levels in RF‐RDN rats (left, 0±0; right, 10±10 ng/g kidney) were markedly decreased compared with levels from sham SHR (left, 130±10; right, 110±10 ng/g kidney). Conclusions These data demonstrate that in hypertensive SHR, bilateral RF‐RDN produces an increase in urinary sodium excretion, which may potentially contribute to the concurrent decrease in BP.Grant Funding Source: Biosense Webster IIS‐175 to DRK & FS; P30 GM103337 to LGN; P20 GM103514 to DRK
A deficiency in the formation of 20‐HETE impairs the myogenic and TGF responses of the Af‐Art of Dahl salt sensitive rats (857.8)
Authors: Ge Ying , Murphy Sydney , Fan Fan , Williams Jan , Falck John , Roman Richard 
Published: June 2021

Previously, we demonstrated that transfer of chromosome 5 containing the CYP4A genes from Brown Norway (BN) rat onto the Dahl S (SS) genetic background (SS.5BN strain) increases the formation of 20‐HETE in renal microvessels and contributes to the antihypertensive effect. Therefore, we hypothesize that a deficiency in the formation of 20‐HETE in the renal vasculature impairs myogenic and TGF responses in the afferent arteriole (Af‐Art) in SS rats. The production of 20‐HETE was 54% lower in renal microvessels of SS rats than in SS.5BNrats. The luminal diameter of the Af‐Art decreased by 15±2% (n=6, p<0.05) in SS.5BN rats when the perfusion pressure was increased from 60 to 120 mmHg, whereas it remained unaltered in SS rats. Administration of an adenosine type 1 receptor agonist (CCPA, 1 µM) reduced the diameter of the Af‐Art in the SS.5BN rats by 44±2%(n=6, p<0.05)., whereas the Af‐Art of SS rats was unaltered SS rats exhibited poor autoregulation of RBF and PGC in vivo, whereas they were well regulated in SS.5BN rats. Administration of a 20‐HETE synthesis inhibitor, HET0016 (1 µM, n=6) completely blocked the myogenic and adenosine responses in the Af‐Art and autoregulation of RBF and PGC in SS.5BN rats but not in SS rats. These data indicated that a deficiency in the formation of 20‐HETE in renal microvessels contributes to the lack of renal autoregulation and development of hypertension in SS rats.Grant Funding Source: This studies were supported by Grant HL36279 and AHA 13POST14220024.
Effects of intermittent heat acclimation on thirst and hypothalamic angiotensin II receptor levels in rats (858.1)
Authors: Johnson Jacob , Barney Christopher 
Published: June 2021

The effects of heat acclimation on thermal dehydration and subsequent water intake are not well understood. In this study, male Sprague‐Dawley rats were exposed to 37.5°C (Intermittent Heat Acclimation ‐ IHA) with or without water or to 25°C with water for 4 hours/day for 7 consecutive days. On day 8, rats from each group were exposed to either 25°C with water or 37.5°C without water. Blood samples were taken for estimation of cellular and extracellular dehydration and the hypothalamus was removed to quantify angiotensin II receptor (AT1 and AT2) levels. Water losses and intakes were measured on days 1 and 7 during the exposure period and for 3 hours following heat exposure. Heat exposure increased water intake during and after exposure, and having access to water during heat exposure increased evaporative water loss but did not alter urine output. IHA decreased evaporative water loss during heat exposure, while not altering urine output during or after heat exposure. IHA also increased water intake in the heat and decreased both water intake following heat exposure and total water intake without changing blood indicators of cellular or extracellular dehydration. Neither IHA nor acute heat exposure altered the levels of AT1 or AT2 receptors in the hypothalamus. IHA reduces evaporative water loss during heat exposure leading to a subsequent reduction in total water intake without altering physiological thirst drives.Grant Funding Source: Supported by a NSF REU Site Award (DBI‐0754293)
Copeptin and norepinephrine during graded hypovolemic stress in women prone to vasovagal syncope (858.6)
Authors: Lindenberger Marcus , Skoog Johan , Alehagen Urban , Länne Toste 
Published: June 2021

Objective: Vasovagal syncope is the most common form of syncope in young individuals, with increased incidence in women. Despite being common, the aetiology is not elucidated. The aim was to study various biomarkers involved in blood pressure homeostasis in women prone to vasovagal syncope.Design and Methods: Graded lower body negative pressure (LBNP) to presyncope was used determine LBNP tolerance index (LTI) in 13 young women prone to vasovagal syncope (VVS) and 15 matched controls (C). Plasma levels of Norepinephrine (P‐NE), Copeptin, a surrogate marker of vasopressin (Cop) and midregion proadenomedullin (MR‐ProADM) was measured before and during graded LBNP.Results: LTI was lower in VVS (163±8) compared to controls (235±8) (P < 0.0001). VVS presented with increased levels of P‐NE at rest as well as LBNP of 30 mmHg, with similar levels at presyncope. P‐NE increase from rest to presyncope was smaller in VVS than in C (P = 0.01). Cop was greater in VVS during LBNP of 30 mmHg, but similar during presyncope. MR‐ProADM was unaffected by graded hypovolemia.Conclusions: Women prone to VVS present with increased levels of P‐NE and Cop during early LBNP, but with similar levels at presyncope, possibly as a result of greater hypovolemic stress at a given LBNP level. To elucidate its role in VVS, these data must be interpreted together with other data during hypovolemia.
Vascular endothelin (ET‐1) mediates skin Na+ storage in response to chronic increases in salt intake (860.13)
Authors: Speed Joshua , Pollock Jennifer , Titze Jens , Pollock David 
Published: June 2021

We have recently implicated extrarenal vascular ET‐1 in the body’s integrated response to a chronic high salt intake by mediating storage of Na+ within the skin. We hypothesize that upregulation of vascular ET‐1 in response to a high salt diet leads to the recruitment of macrophages and lymphocytes to the interstitium of the skin, which promote lymph hyperplasia, all of which provide a buffer for extracellular Na+ homeostasis. In the present study, we determined if vascular endothelial cell ET‐1 knockout mice (VEET KO) have reduced vascular cell adhesion molecule expression and increased skin Na+ storage in response to a high salt diet. After 2 weeks of a high NaCl (4%) diet, VEET KO mice have higher total skin Na/water ratio than floxed controls (0.112±0.007 vs. 0.096±0.003 mmol/ml respectively). Floxed control mice have elevated ET‐1 mRNA in the aorta compared to animals on low salt (1.38±0.21 vs. 1.05±0.14 fold change respectively, n=6), a response that was completely blunted in VEET KO mice (1.07±0.12 vs. 1.05±0.16 fold change, n=5). There was no change in vascular cell adhesion molecule‐1 between groups. These data support our hypothesis that vascular endothelial derived ET‐1 plays a critical role in mediating skin storage of Na+ in response to a high salt intake.Grant Funding Source: Supported by NHLBI and AHA
Oxidative stress signaling in response to CD4+T cells stimulated via placental ischemia play an important role in hypertension during preeclampsia (860.14)
Authors: Scott Jeremy , Wallace Kedra , Cornelius Denise , Amaral Lorena , Moseley Janae , Chapman Krystal , LaMarca Babbette 
Published: June 2021

Preeclampsia (PE) is associated with hypertension, oxidative stress, and chronic inflammation. The RUPP rat model of PE and normal pregnant (NP) recipient rats of RUPP CD4+T cells exhibit much of the disease pathology. Reactive oxygen species (ROS) could be released from monocytes or neutropils, however the objective of this study was to determine if RUPP CD4 T cells are a cellular source of ROS and hypertension (MAP) and during pregnancy. CD4+Tcells from RUPP rats were injected into NP recipients on gestational day (GD)13; GD19 MAP, urine and tissues were analyzed. Prior to injection RUPP CD4+ T cells secreted more myleoperoxidase compared to NP (116.9+15.2 vs. 48.5+8.3 ng/mg/mL; p=0.003). Placental NADPH oxidase mediated ROS in RUPP rats was 830.6+68, 726.2+43.73 in NP + RUPP CD4+ T cells and 420.7+51.4 RLU/min/mg in NP rats; p=0.009 and p=0.004, respectively. MAP was 100+2 in NP rats, 126+4 in RUPP rats (p=0.0001) and 118+4mmHg in NP+RUPP CD4+ T cell rats (p=0.002) which was attenuated with apocynin; 111+2 in RUPP + apocynin; 102+3 mmHg in NP + RUPP CD4+ T cells (p=0.01). These data suggest that CD4+Tcells are an important source of ROS mediating hypertension in response to placental ischemia.Grant Funding Source: NIH NICHD; APS STRIDE
IL‐10 supplementation suppressed hypertension and inflammation in response to placental ischemia during pregnancy (860.17)
Authors: Harmon Ashlyn , Paige Adrienne , Cornelius Denise , Wallace Kedra , Thomas Alexia , Scott Jeremy , Moseley Janae , LaMarca Babbette 
Published: June 2021

Women with preeclampsia (PE) develop hypertension, proteinuria, increased pro‐inflammatory and decreased regulatory immune responses (Tregs, IL‐10) contributing to increased local ET‐1. The RUPP rat model of PE exhibits a similar increase in MAP, immune imbalance and ET‐1 as women with PE. We hypothesized that IL‐10 supplementation in RUPP rats will restore T cell balance, decrease MAP and inflammation. IL‐10 was administered intraperitoneally via osmotic pumps to RUPP rats on day 14 of gestation following the RUPP procedure. On day 18 carotid catheters are inserted, and on day 19 MAP, pup weights, serum and tissues are collected. MAP in NP rats was 91+/‐2, RUPP was 122+/‐2 which decreased to 106+/‐2 mmHg in RUPP+IL‐10. Circulating CD4+ T cells were 14% gated cells in RUPP and 8% gated cells RUPP+IL‐10. IL‐6 was 33+/‐5 NP, 238+/‐96 RUPP, 40+/‐10 pg/mL RUPP+IL‐10; TNF‐α was 14.73+/‐3 NP, 69+/‐ 19 RUPP, 20+/‐11 pg/mL RUPP+IL‐10, and placental ET‐1 was 2.5 fold higher in RUPP but only 1.4 fold higher in RUPP+IL‐10 compared to NP rats. These data suggest an important role for IL‐10 supplementation to balance the inflammatory response and improve blood pressure and ET‐1 production associated with placental ischemia of pregnancy.Grant Funding Source: Supported by RO1HD067541 & T32HL105324
Stimulation of a neuroimmune pathway protects from hypertension (860.22)
Authors: Mathis Keisa 
Published: June 2021

Vagus nerve stimulation can suppress cytokine release from splenic immune cells and therefore reduce systemic inflammation through a pathway involving nicotinic acetylcholine receptors (α7nAChR). We tested whether activation of this ‘cholinergic anti‐inflammatory pathway’ protects from hypertension during systemic lupus erythematosus (SLE), a chronic autoimmune inflammatory disorder with autonomic dysfunction, renal injury, and hypertension. A female mouse model of SLE that develops hypertension (NZBWF1) was infused with nicotine hydrogen tartrate salt (2 mg/kg/day, subcutaneously) or saline for 7 days via osmotic minipumps. Splenic TNF‐α protein expression was higher in SLE mice (1.37±0.06) than controls (0.44±0.08; p<0.001), nicotine‐treated controls (0.48±0.05; p<0.001), and nicotine‐treated SLE mice (1.09±0.06; p=0.041). Albumin excretion rate (μg/day) was increased in SLE mice compared to controls (157±62 vs. 59±15; p=0.038). Nicotine prevented the rise in albuminuria in SLE mice (112±42; p=0.013), but had no effect in controls (46±8). Blood pressure (mmHg) was increased in SLE mice compared to controls (140±4 vs. 114±2; p<0.001). Nicotine prevented the rise in blood pressure in SLE mice (129±4; p=0.022), but did not alter blood pressure in controls (121±3). These data suggest the anti‐inflammatory effects of nicotine may prevent hypertension in mice with SLE and that the novel cholinergic anti‐inflammatory pathway may be an important target in patients with hypertension associated with chronic inflammatory diseases.Grant Funding Source: Supported by F32HL114272 and P01HL051971
Hypothalamic PVN Gαi2 protein‐mediated regulation of renal NE turnover and sodium homeostasis: implications for the pathophysiology of salt‐sensitive hypertension (860.23)
Authors: Wainford Richard , Mahne Sarah , Kuwabara Jill 
Published: June 2021

Aim: These studies examined the direct role of PVN Gαi2 proteins, which are up‐regulated during high‐salt intake in Sprague‐Dawley (SD) rats, in the regulation of water & electrolyte homeostasis, MAP and CNS/renal norepinephrine (NE) levels during high salt‐intake.Methods: Groups of male SD rats received a bilateral PVN infusion of a scrambled (S) or Gαi2 oligodeoxynucleotide (ODN‐300ng/side/day) and a 7‐day normal 0.4% (NS) or high 8% NaCl (HS) diet. On day‐7 24h Na+ balance was assessed. In sub‐groups MAP, estimated blood volume (EBV), estimated plasma volume (EPV), plasma NE levels and PVN and kidney NE turnover were assessed (N=6/gp/study).Results: In S infused rats HS did not alter sodium homeostasis (24h Na+ balance [meq] NS 0.7±0.3 vs HS 0.9±0.3), MAP (MAP [mmHg] NS 126±3 vs HS 127±3) or EBV and EPV. In S infused rats HS intake suppressed plasma NE content (plasma NE [nmol/L] NS 72±4 vs HS 40±5, P<0.05), kidney NE content (NE [pg/mg] NS 586±36 vs HS 496±31, P<0.05) and NE turnover in the PVN. HS intake in rats receiving a Gαi2 infusion evoked sodium retention (24h Na+ balance [meq] NS 0.6±0.2 vs HS 2.5±0.4 P<0.05), hypertension (MAP [mmHg] NS 127±3 vs HS 146±4, P<0.05) and increased blood and plasma volume (EPV [ml] NS 10.9±0.4 vs HS 11.8±0.4, P<0.05; EBV [ml] NS 21.1±0.5 vs HS 22.4±0.3, P<0.05). In Gαi2 infused rats HS intake increased plasma NE content (plasma NE (NE [nmol/L]; NS 67±7 vs HS 105±11, P<0.05), kidney NE content (NE [pg/mg] NS 614±48 vs HS 823±59, P<0.05) and kidney NE turnover (NE turnover rate [pg/mg/hr] NS 7.5±0.6 vs HS 20.3±1, P<0.05) while suppressing PVN NE turnover.Conclusion: Impairment of PVN Gαi2 signal transduction during high salt‐intake results in dysregulation of renal NE content and turnover. This imbalance likely drives sodium & fluid retention stimulating the development of hypertension. These data highlight the interaction between the CNS and kidney, and the role of the sympathetic nervous system, in the long‐term regulation of MAP.Grant Funding Source: Support by R01HL107330 & K02HL112718A1
Src‐kinase mediates angiotensin II‐induced potentiation in TRPV4 agonist‐evoked calcium transients in hypothalamic immortalized neuronal cell line 4B (860.25)
Authors: Saxena Ashwini , Bachelor Martha , Carreno Flavia , Cunningham J 
Published: June 2021

We have previously demonstrated that in bile duct ligated rats, an animal model of inappropriate vasopressin (AVP) release, TRPV4 protein expression and membrane trafficking is increased in AVP neurons. Here, we used an in vitro approach with an immortalized neuronal AVP expressing cell line (4B neurons) to investigate the possible regulation of TRPV4 by angiotensin II (Ang II). We characterized the presence of TRPV4 mRNA and protein in 4B cells. After Ang II (100nM;1 hr) treatment significantly increased TRPV4 levels in crude membrane fractions (p<0.001) and tyrosine phosphorylation of TRPV4 (p<0.001). Using calcium sensitive dye Fura‐2AM, we noted that Ang II treated cells exhibited increased calcium transients in response to TRPV4 agonist, GSK1016790A (20nM, p<0.05). This increase was blocked by the Losartan (Ang II receptor antagonist) and Src‐kinase inhibitor, PP2, but not by its analog PP3. Our data indicate that Ang II may alter the phosphorylation status of TRPV4 through Src‐kinases.Grant Funding Source: Supported by: R01 HL62569
VAMP8 knockout mice show enhanced renin release and content, kidney damage and salt sensitivity (860.5)
Authors: Mendez Mariela , Haque Mohammed , Ortiz Pablo 
Published: June 2021

The vesicle fusion SNARE protein VAMP8 mediates trafficking of aquaporin 2 in kidney collecting ducts. Gene deletion of VAMP8 in mice (V8‐KO) resulted in polyuria and enhanced plasma renin. Renin is stored in granules in juxtaglomerular (JG) cells and its release is mediated by SNARE proteins. In other endocrine cells, VAMP8 mediates granule maturation and constitutive exocytosis. We found that VAMP8 is expressed in JG cells. However, it is not known whether VAMP8 regulates renin release from JG cells or the enhanced plasma renin in V8‐KO is due to compensation for volume loss. We hypothesized that VAMP8 mediates renin granule maturation and constitutive renin release from JG cells. Primary cultures of JG cells from V8‐KO showed enhanced renin and pro‐renin protein expression compared to wild type (WT) (n=5). Baseline renin release from JG cells was 5‐fold higher in V8‐KO than WT (WT=0.06±0.01; KO=0.3±0.05 μgAngI/hr/mg prot.; p<0.05). Immunolabeling of renin and confocal imaging showed enlarged granules and vacuoles in JG cells from V8‐KO. Similar results were observed in V8‐KO JG cells by electron microscopy. Kidney histology showed enhanced renal fibrosis and glomerular sclerosis in V8‐KO (n=4). Despite the higher release of renin and kidney damage, baseline blood pressure in V8‐KO was similar to WT (mmHg: WT=122±3.4; V8‐KO=121±4.5). A high salt diet (1% NaCl drinking water) increased blood pressure in V8‐KO mice by 16±5 mmHg (p<0.05) but not in age matched WT controls. We concluded that VAMP8 plays an inhibitory role in renin release, most likely by mediating normal granule maturation. VAMP8 may regulate blood pressure by inhibiting renin release during a high salt diet. VAMP8 is protective against kidney damage, but the mechanism is unclear.Grant Funding Source: Supported by AHA and NIH
Endothelin, Ang II, vasopressin and osmolality regulate hyaluronan turnover by renomedullary interstitial cells suggesting an involvement of this matrix component in fluid handling (860.9)
Authors: Hansell Peter , Palm Fredrik , Takahashi Tomoko , Ikegami‐Kawai Mayumi , Stridh Sara 
Published: June 2021

The content of the matrix component hyaluronan (HA) change in the medullary interstitium in relation to hydration status in vivo: elevated during hydration, reduced during dehydration suggesting a role in fluid handling by affecting interstitial fluid flux. We examined the effect of osmolality and fluid regulating hormones on HA‐turnover by RMIC in culture. Reducing media osmolality to simulate hydration, increased supernatant HA 4‐fold. Cell HA synthase (HAS) 2 and Hyaluronidase (Hyal) 2 mRNA expressions were unaltered while Hyal 1 mRNA was reduced by 35%. Supernatant Hyal activity was reduced by 44%. An inhibitor of Hyal activity (Asc‐P) elevated HA to similar high levels as low osmolality. AngII reduced HA by 58% and combined treatment with vasopressin reduced HA even further (69%). HAS and Hyal mRNA were stable while Hyal activity increased by 38% by AngII and 67% by the combination. Low dose endothelin (ET, 10‐10M) increased HA 3‐fold which was inhibited by ET‐B receptor blocker BQ788. On the contrary, high dose ET (10‐6M) reduced HA by 47%. The ET‐A receptor antagonist BQ123 not only reversed the reducing effect of high dose ET on HA but elevated it to the same level as low dose ET suggesting importance of ET‐B receptors. The study demonstrates a regulatory influence of osmolality and fluid regulating hormones on HA turnover, supporting the concept of an involvement of medullary interstitial HA in renal fluid handling by affecting interstitial permeability.Grant Funding Source: Supported by the Swedish Research Council‐Medicine
Maintenance and termination of atrial fibrillation in a patient‐specific model (861.1)
Authors: Gonzales Matthew , Vincent Kevin , Rappel Wouter‐Jan , Narayan Sanjiv , McCulloch Andrew 
Published: June 2021

Atrial fibrillation (AF) is the most common arrhythmia in the United States and is a risk factor for stroke and cardiac dysfunction. Radiofrequency (RF) ablation has shown great promise for improving outcomes for drug‐resistant AF. However, readmission rates remain high, and improving surgical strategies for targeted RF ablation is subject of intense research. In this study a patient‐specific biatrial finite element model of cardiac electrophysiology is used to explore mechanisms of AF maintenance and termination. Results demonstrate that with normal physiological anisotropy ratios and effective refractory periods (ERPs) of atrial myocytes, free wavelets do not attach to small (~1 cm), inexcitable regions and become rotors. With the depressed excitability, depressed anisotropy, and shorter ERPs present in AF, stationary rotors form around large (>1 cm) inexcitable regions and have a small spatial excitable gap; in contrast, meandering rotors are stabilized by small (<1 cm) inexcitable regions but anchor only transiently to them, colliding with their waveback and drifting until a region of space recovers and allows them to pivot. Based on these results, simulated RF ablation scars could terminate AF by two mechanisms: One, RF lesions increase the inexcitable region size for both meandering and stationary rotors, creating or widening a spatial excitable gap and allowing impingement and extermination of the rotor by an external wave. Two, the RF lesions increase the AF cycle length by increasing the path length of a rotor, in turn both regularizing the atrial activation sequence and decreasing global fractionation, promoting spontaneous termination.Grant Funding Source: Supported by NIH grants HL96544 (ADM), HL083359 (SMN, WJR), and EB009380