bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of mineralocorticoid receptors in the dorsal hindbrain enhances baroreflex sensitivity (1130.4)
Authors: Backes Iara , Clifton Rebekah , Scheuer Deborah , Adler Gail 
Published: June 2021

This study tested the hypothesis that chronic blockade of mineralocorticoid receptors (MR) in the dorsal hindbrain (DBH) enhances spontaneous baroreflex sensitivity (sBRS) in male Sprague‐Dawley rats subjected to chronic variable stress (CVS) for 2 weeks. Rats were instrumented with radiotelemetry transmitters to obtain cardiovascular data, and pellets made of cholesterol (Chol) or the MR antagonist spironolactone (SPL) were implanted on the DBH (n=5‐6 per group). Two weeks later rats were subjected to CVS, which included insulin‐induced hypoglycemia on the first day of stress. SPL significantly (P<0.05) increased the sBRS prior to (2.1±0.1 vs. 1.5±0.2 ms/mmHg in SPL vs Chol rats) and after 2 weeks of CVS (2.1±0.1 vs. 1.6±0.2 ms/mmHg in SPL vs Chol rats). Neither CVS nor hypoglycemia altered sBRS. Blood glucose was measured at 20, 40, 60, 90, 120 and 180 min after insulin (7‐8 U/kg, i.p.) was administered to non‐fasted rats. Glucose reached a nadir at 2 hr, when levels were significantly higher in SPL compared to Chol rats, (37±3 vs.28±1 mg/dl, P<0.05). The results indicate that chronic blockade of DHB MR enhances sBRS and blunts the hypoglycemic effect of insulin.Grant Funding Source: Supported by NIH #HL076807 and AHA #GRNT4460047
Enhanced leptin‐TRPC signaling in the hypothalamus contributes to the exaggerated sympatho‐excitation in type 2 diabetic rats (1130.9)
Authors: Zheng Hong , Liu Xuefei , Li Yulong , Patel Kaushik 
Published: June 2021

Accumulated evidence indicates that type 2 diabetes (T2D) is associated with enhanced sympathetic activation. Transient receptor potential canonical channels (TRPC) have been found in pro‐opiomelanocortin neurons and activated by leptin. The present study was conducted to investigate the role for leptin‐TRPC signaling in centrally mediated sympathetic response in rats with T2D. In high‐fat diet and low‐dose strepzotocin (30mg/kg)‐induced T2D rats, mRNA levels of TRPC subtype including TRPC1, 4, 5 and 6 were significantly increased in the paraventricular nucleus (PVN) and arcuate nucleus (ARCN) compared to control rats (n=8/group). Whole‐cell patch‐clamp was conducted in primary cultured hypothalamic neurons to record TPPC currents. Neurons from T2D rats had significant increased TRPC currents (about 2 folds to the control). In anaesthetized condition, microinjections of leptin (5ng~100ng) into the ARCN and PVN induced increases in renal sympathetic nerve activity and blood pressure. These effects were significantly blocked by pre‐microinjections of TRPC inhibitors (2APB and SKF96365). In cultured neuronal cell NG108, pre‐incubation with leptin (0.625~2.5μM) for 24hrs induced significant increases of TRPC mRNA expressions (TRPC1, 4 and 5). Taken together, these data suggest that within the hypothalamic nuclei, leptin‐induced sympatho‐excitation in T2D maybe mediated through an activation of TRPC. Supported by NIH grant DK82956.Grant Funding Source: NIH DK82956
A neurophysiological study of the medullary sympathetic pathway to the adrenal gland (1131.7)
Authors: Verberne Anthony , Korim Willian , Sabetghadam Azadeh 
Published: June 2021

Neurons in the rostral ventrolateral medulla (RVLM) control adrenaline secretion from the adrenal gland and participate in glucose homeostasis. Here, we examined sympathetic evoked responses recorded from the adrenal sympathetic nerve in response to intermittent stimulation of the RVLM. All experiments were performed using isoflurane/urethane‐anaesthetised, artificially‐ventilated, paralysed, male Sprague‐Dawley rats. The RVLM was first identified by extracellular single unit recording combined with field potential mapping of the facial nucleus. We compared the latencies of the evoked adrenal sympathetic nerve (ASNA) response to the lumbar sympathetic nerve (LSNA) response upon electrical stimulation of RVLM (0.5 Hz, 1 ms pulse width, 50‐300 μA) after conversion to urethane (1.4 g/kg, i.v.). RVLM stimulation elicited an evoked ASNA response that depended on whether the recording was primarily pre‐ or post‐ganglionic activity as judged by the effect of the ganglion blocker hexamethonium (Hex; 20‐40 mg/kg, i.v.). Pre‐ganglionic ASNA consisted of an early peak (latency ‐ 79±9 ms, n=4) and a late peak (latency ‐ 149±6 ms). Lumbar sympathetic nerve activity exhibited a prominent early peak (latency ‐ 87±7 ms; n = 5) that was eliminated by Hex. Pre‐ganglionic ASNA was reduced by 62 % after intrathecal kynurenate (0.5 μmole/10 μl; P<0.01, late peak, n=3). The early peak may represent sympathetic vasomotor activity in both the adrenal and lumbar sympathetic nerves. However, the late sympathetic response noted in the adrenal nerve is mediated by a glutamatergic input and may be involved in the control of catecholamine secretion from adrenal chromaffin cells.Grant Funding Source: National Health and Medical Research Council of Australia
Effects of digitoxin treatment on reflex cardiovascular control in rats with heart failure (1132.2)
Authors: Fardin Núbia , Antonio Ednei , Montemor Jairo , Tucci Paulo , Campos Ruy 
Published: June 2021

There is evidence that digitalis promote changes in the autonomic and reflex control of the cardiovascular system and enhances survival in rats with Heart Failure (HF). The major aim of the present study was to evaluate the effects of digitoxin treatment on basal renal sympathetic nerve activity (rSNA) and on the reflex control of the cardiovascular system by the arterial baroreceptors and cardiopulmonary reflex in HF rats. Male Wistar rats (±200g) were divided into two experimental groups: HF and HF treated with digitoxin in the diet for 60 days (1mg/Kg/day) (HF+DIG). A significant increase in rSNA were found in HF (190 ± 29pps; N= 5) compared to control rats (98 ± 14pps, N=5). Digitoxin treatment leads to a significant decrease and normalizes rSNA in HF+DIG rats (98 ± 14pps, N= 7). The baroreflex sensitivity for the control of rSNA was significantly decreased by treatment (slope: ‐0.69 ± 0.10pps/mmHg, N= 7) when compared to HF group (slope: ‐2.66 ± 0.12pps/mmHg, N= 5). A similar result was found for the cardiopulmonary reflex, digitoxin reduced the fall in heart rate (HF: 180 ± 7bpm, N=8; HF+DIG: ‐126 ± 14bpm, N=9) in response to acute phenylbiguanide administration. Altogether the results demonstrate that the fall in rSNA in response to digitoxin in HF rats is not related to improvement in the reflex control of the cardiovascular system. Central actions of digitoxin may explain the sympathoinhibitory effects of digitalis.Grant Funding Source: CAPES, CNPq and FAPESP (2009/54225‐8)
Device‐guided slow deep breathing in essential hypertension: is cardiac or sympathetic baroreflex sensitivity altered? (1132.7)
Authors: Shantsila Alena , Adlan Ahmed , Lip Gregory , Pickering Anthony , Paton Julian , Fisher James 
Published: June 2021

The influence of device‐guided slow deep breathing (SDB; RESPeRATE□) on arterial baroreflex control of the heart and muscle sympathetic nerve activity (MSNA) in essential hypertension patients remains unclear. To address this, respiratory rate, partial pressure of end‐tidal carbon dioxide (PETCO2), MSNA (microneurography), heart rate (HR) and blood pressure (BP: Finometer) were monitored in 8 hypertensive patients (55±14 years, BMI 28±3 kg/m2, 152±26/71±11 mmHg [systolic/diastolic BP], duration of hypertension 6.4±6.7 years; mean±SD) during 10 min of normal breathing and 10 min of SDB. Cardiac baroreflex sensitivity (sequence technique) and spontaneous arterial baroreflex control of MSNA burst incidence were calculated offline. As expected, SDB decreased respiratory rate (13±4 to 6±1 breath/min, P=0.001), whereas PETCO2 (P=0.22), and mean BP (98±14 to 97±13 mmHg, P=0.11) were unchanged. MSNA burst incidence tended to fall during SDB (median with interquartile range from 46 [34‐56] to 40 [31‐48] bursts per 100 heart beats, P=0.12), however neither cardiac nor sympathetic baroreflex sensitivity were altered (P>0.05). In conclusion, acute device‐guided SDB does not appear to modify cardiac and sympathetic baroreflex sensitivity in patients with essential hypertension.Grant Funding Source: Supported by British Heart Foundation
Activities in a single sensory fiber of the aortic depressor nerve were derived from multiple encoders (1132.8)
Authors: Liu Jun , Song Nana , Tian Shifu , Guardiola Juan , Proctor Mary , Yu Jerry 
Published: June 2021

Arterial baroreceptors, resembling airway slowly adapting receptors (SARs) that regulate breathing, play a very important role in the regulation of blood pressure. However, the sensory processing mechanisms at the cellular level remain unclear. Recently, a SAR unit was found to contain multiple encoders. Therefore, we hypothesize that a barosensory unit is the same. We used immunofluorescent approach to examine the baroreceptor structure in rabbit aortic arches morphologically. A single myelinated axon may connect with multiple structures, clustered in the aortic arch near the bifurcation or origin of the common carotid and subclavian arteries, forming a network. Physiologically, we recorded single‐unit activity in the depressor nerve in anesthetized rabbits and examined their response to phenylephrine. The unit activity increased progressively as blood pressure (BP) increased and decreased abruptly (deactivation) after the BP attained a plateau for about 2 min. Their activity became slow first (indicating multiple encoders) and subsequently ceased. The unit could be reactivated by lowering BP and deactivated again by raising BP. Since baroreceptors resemble SARs morphologically and electrophysiologically, we conclude that a single barosensory unit contains multiple encoders. Thus, the sensory unit is not only a transducer but also a processor that integrates a significant amount of information.Grant Funding Source: VA Merit Review PULM‐029‐10S
Hypertension impairs spontaneous baroreflex heart rate control during exercise and muscle metaboreflex activation (1132.9)
Authors: Augustyniak Robert , Spranger Marty , Abu‐Hamdah Rania , Kaur Jasdeep , Hammond Robert , Sala‐Mercado Javier , Ichinose Masashi , O'Leary Donal 
Published: June 2021

Spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) is reduced in proportion to exercise intensity and magnitude of MMA. In hypertension (HTN), while SBRS is reduced at rest, the effect of exercise and MMA are unknown. In eight conscious dogs we measured SBRS in the control of HR (sequence method) at rest, during mild dynamic exercise, and during MMA (via imposed reductions of hindlimb blood flow), in the same animals before and 38±7 days after induction of HTN (via unilateral partial renal artery occlusion). HTN increased resting mean arterial blood pressure from 94±3 to 142±14 mmHg. In control, with the transition from rest to exercise, SBRS decreased from ‐4.01±0.77 to ‐2.38±0.61 bpm/mmHg and reduced further to ‐1.78±0.43 with MMA. In HTN, SBRS was significantly reduced at rest (‐2.38±0.34), during exercise (‐1.05±0.12) and MMA (‐0.90±0.14).We conclude that in HTN SBRS in the control of HR is impaired to similar degrees at rest, during exercise and MMA.Grant Funding Source: HL‐55743 and HL‐095819
Changes in mitochondrial metabolism and morphology contribute to sepsis‐associated acute kidney injury (1134.10)
Authors: Thomas Joanna , Ayoyama Koji , Nourbakhsh Noureddin , Singh Prabhleen 
Published: June 2021

Acute Kidney Injury (AKI) is commonly seen in septic patients, but there are no effective treatments to prevent or treat it. New perspectives on the pathogenesis of AKI in sepsis are needed to improve the current standard of treatment. We examined renal mitochondrial function and expression of proteins with known roles in mitochondrial function and dynamics in the cecal ligation and puncture (CLP) model of sepsis in rats. At 24 hrs post CLP or sham surgery, kidney tissue and mitochondria were isolated for protein expression analyses and mitochondrial functional assays including mitochondrial oxygen consumption (QO2), ATP generation and reactive oxygen species (ROS) generation. Data represents mean ± SEM.In isolated mitochondria, QO2 rates were higher in CLP compared to sham; with the largest difference observed during state 3 (199.9 ± 31.6 pMol/min vs. 163.2 ± 28.81 pMol/min, p<0.05). However, ATP generation was significantly lower in the mitochondria from CLP kidneys. With western blot expression, we found increased expression of mitochondrial fission proteins DRP1 (1.9‐fold higher in CLP, P<.0004) and Fis1 (trend for higher expression) in CLP kidneys. We also observed decreased expression of PGC‐1α, a key transcription factor in mitochondrial biogenesis. Analysis of the expression of the expression of the ETC complexes in the mitochondrial fraction showed a 25% reduction (P 蠄 .001) in Complex Va and Complex III in CLP mitochondria. In conclusion, our data indicate significant increase in renal oxidative metabolism but without the associated ATP generation and reduction in the expression of ETC complexes. Mitochondrial analyses reveal increased mitochondrial fission but with reduced biogenesis, indicating increased mitochondrial stress. Additional morphological and functional analyses are being conducted. We are also evaluating mechanisms underlying the altered mitochondrial function to identify potential therapeutic targets for the treatment of kidney injury during sepsis.Grant Funding Source: NIH
Tumor necrosis factor‐α supression rescues glutathione peroxidase activity in kidney of insulin resistant rats (1134.12)
Authors: Carter Matthew , Lee Andrew , Rodriguez Ruben , Thorwald Max , Ortiz Rudy , Nishiyama Akira 
Published: June 2021

The interactions between reactive oxygen species (ROS) production and kidney nephropathy in metabolic syndrome are not well described. This study assessed the effects of blocking 1) renin‐angiotensin system (RAS), 2) tumor necrosis factor‐alpha (TNFα)‐mediated inflammation, 3) and non‐RAS‐mediated hypertension on the activity of the antioxidant enzymes, glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD) in the kidney of insulin resistant (IR), Otsuka‐Long‐Evans‐Tokushima‐Fatty (OLETF) rats. Lean and obese rats (n = 5‐7/group) were randomly assigned to the following groups: 1) untreated Long‐Evans‐Tokushima‐Otsuka (LETO) (lean, strain control ), 2) untreated OLETF, 3) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg/d x 10 wk), 4) OLETF + TNFα blocker (ETAN) (1.25 mg entanercept/kg/d x 10 wk), 5) OLETF + calcium channel blocker (CCB) (3 mg amlodipine/kg/d x 10 wk), and 6) OLETF + ARB+ ETAN (COMBO) (same doses x 10 wk). OLETF exhibited a 23% decrease (41 ± 4 vs. 32 ± 3 nmol/min/ml) in mean GPx activity. TNFα blockade completely recovered the IR‐associated decrease in GPx activity (45 ± 4 nmol/min/ml) demonstrating that TNFα contributes to the dysregulation of antioxidant enzymes in the IR kidney. Catalase and SOD activities, while elevated, were not different among groups suggesting that the dysregulation of antioxidant enzymes is selective during IR conditions.Grant Funding Source: APS Teacher Researcher
Disruption of cyclooxygenase type 2 exacerbates the progression of oxidative stress during obstructive nephropathy (1134.2)
Authors: Nilsson Line , Madsen Kirsten , Jensen Boye , Norregaard Rikke 
Published: June 2021

Renal oxidative stress is increased in response to ureteral obstruction. In vitro, COX‐2 activity contributes to antioxidative protection. Here, we test the hypothesis that COX‐2 activity counters oxidative stress in an in vivo setting of obstructive nephropathy. The progression of renal oxidative stress was investigated in COX‐2‐/‐ and WT mice subjected to 3 days of unilateral ureteral obstruction (UUO).Following UUO, kidney weight and functional parameters were analysed. Using immunoblot analysis, we examined the oxidative stress marker, heme oxygenase‐1 (HO‐1), antioxidant enzymes, superoxide dismutase 1 and 2 (SOD1 and ‐2), and caspase 3 in renal cortex and inner medulla (IM).Plasma creatinine was increased in response to UUO, however, COX‐2‐/‐ had more increased plasma creatinine compared to WT. COX‐2 mRNA level was increased in WT mice subjected to UUO and undetectable in COX‐2‐/‐ mice. HO‐1 protein abundance increased in response to UUO and was further increased in COX‐2‐/‐ mice. Both SOD1 and SOD2 protein levels were downregulated in IM and cortex in WT mice after UUO. COX‐2 knockout prevented downregulation of SOD2 in both cortex and IM whereas SOD1 reduction was only attenuated in cortex. Cortical caspase 3 was increased in response to UUO, and further increased in COX‐2‐/‐ mice.In summary, disruption of COX‐2 exacerbates oxidative stress and increases apoptosis markers in response to obstruction.
Effects of 17β‐estradiol replacement in a model of renal ischemia in the ovariectomized female apolipoprotein E knockout mouse (1135.2)
Authors: Li Lijun , Ji Hong , Holloway Chelsee , Sandberg Kathryn , Ecelbarger Carolyn 
Published: June 2021

Cardiovascular disease is a major cause of morbidity and mortality in postmenopausal women. 17ß‐estradiol (E2) replacement in ovarian hormone deficient rodents inhibits renal and vascular damage in models of ischemia and attenuates inflammatory responses in models of atherosclerosis. We hypothesized that E2 replacement in ovariectomized (OVX) female atherosclerotic mice would protect against vasculature and kidney damage in renal ischemia by attenuating inflammation. Left renal artery incomplete ligation and ovariectomies were performed on 12‐week‐old, female apolipoprotein E (ApoE) knockout (KO) mice and either E2 (2 μg/day x 60 days) or placebo (P) pellets (n = 6/group) were inserted subcutaneously. After 60 days, animals were euthanized and kidneys, blood, and aortic and carotid vessels were obtained. E2 replacement attenuated the ischemia‐induced reduction in left kidney weight [g: OVX + E2, 0.13 ± 0.017 vs. OVX + P, 0.058 ± 0.016; p < 0.02]. E2 treatment had no effect on the contralateral right kidney weight or on body weight. E2 replacement lowered plasma insulin by 18% [µg/L: OVX + E2, 0.33 ± 0.009 vs. OVX + P, 0.40 ± 0.023; p<0.02] and plasma triglycerides by 46% [µg/dL: OVX + E2, 30.3 ± 3.5 vs. OVX + P, 56.6 ± 8.4; p<0.02]. Plasma interleukin‐6 (IL‐6) was increased by E2 [pg/ml: OVX + E2, 156 ± 67 vs. OVX + P, 16.7 ± 7.0; p<0.05]. E2 treatment attenuated the ischemia‐induced glomerular injury, tubular atrophy, interstitial fibrosis and inflammation and neointima proliferation in the thoracic and abdominal aorta and carotid artery. These findings suggest E2 markedly protects the ovarian‐hormone‐deficient atherosclerotic female from the renal and vascular damage induced by renal ischemia. Possible protective means include improvement of the metabolic profile, and a near 10X increase in mean circulating levels of the potentially anti‐inflammatory cytokine, IL‐6.Grant Funding Source: Supported by NIH DK082507 and Marriott Fellowship
T cell‐dependent hypertension is attenuated in female mice during angiotensin II infusion (1136.10)
Authors: Pollow Dennis , Romero‐Aleshire Mellisa , Uhrlaub Jennifer , Nikolich‐Zugich Janko , Hay Meredith , Brooks Heddwen 
Published: June 2021

Previous studies have shown that the adaptive immune system is required for the development of Ang II‐induced hypertension in male mice. Here we determine if there are sex differences in the ability of the adaptive immune system to induce hypertension and alter T cell infiltration and renal dysfunction in response to Ang II infusion. Male and female RAG‐1‐/‐ mice, which lack both T and B cells, received adoptive transfer of male CD3+ T cells 3 weeks prior to Ang II infusion (490ng/kg/min 14d) (n=8). Controls received T cells or Ang II. Blood pressure was monitored via tail cuff. In the absence of T cells, Ang II induced a small increase in systolic blood pressure (SBP) in males &amp; females (Δ10.9 vs. Δ14.1mmHg). After adoptive transfer, Ang II induced a significant increase in SBP in males (Δ36.8mmHg, p< 0.01), while females were no different from Ang II‐only controls (Δ16.9mmHg). PAS staining identified that Ang II infusion significantly increased glomerular hypertrophy in both males and females, independent of T cells; glomerular area was significantly greater in males vs females, at baseline. Renal CD3+, CD4+, CD8+, and Foxp3+ lymphocyte infiltration was significantly greater in males compared to females, independent of Ang II. These results suggest that females are protected from Ang II‐induced T cell‐dependent hypertension, and that this protection may involve sex differences in T cell‐infiltration of the kidney.Grant Funding Source: Supported by Training Grant HL007249 (J. Burt), UA Sarver Heart Center, ARCS Foundation
High salt intake aggravates aortic dysfunction in rats with adenine‐induced chronic renal failure (1136.13)
Authors: Nguy Lisa , Nilsson Holger , Guron Gregor 
Published: June 2021

Rats with adenine‐induced chronic renal failure (ACRF) develop a reduced rate of relaxation, and increased stiffness of the aorta. The aim of this study was to investigate the effects of 2 weeks of high NaCl intake on vascular function in rats with ACRF.Male Sprague‐Dawley rats received either chow containing adenine (ACRF) or were pair‐fed a control diet (Controls, C). Two weeks prior to sacrifice animals were randomized to diet containing either normal salt (0.6% NaCl, NS) or high salt (4% NaCl, HS), resulting in four groups: C‐NS, C‐HS, ACRF‐NS and ACRF‐HS (n=11‐15 per group). Animals were sacrificed at 7‐10 weeks after study start and mesenteric arteries and thoracic aorta were analyzed with wire myograph.Animals with ACRF showed significant increases in serum creatinine and systolic blood pressure that was aggravated by high NaCl intake (138±14, 164±10, 152±7 and 202±14 mmHg in groups C‐NS, ACRF‐NS, C‐HS and ACRF‐HS, respectively). A decreased sensitivity to norepinephrine was found in mesenteric arteries of ACRF‐HS rats (P<0.05). In the thoracic aorta, the sensitivity to both sodium nitroprusside (SNP) and acetylcholine (ACh) were reduced only in ACRF‐HS animals (P<0.05). Furthermore, the ACRF‐HS group exhibited a marked decrease in aortic relaxation rate compared to ACRF‐NS animals (P<0.01).In rats with ACRF two weeks of high NaCl intake reduced the sensitivity to ACh and SNP in the thoracic aorta and aggravated the impairment in relaxation rate whereas vasodilator responses were unaffected in resistance arteries. These results indicate an abnormality in vascular smooth muscle function specifically in the thoracic aorta of ACRF animals that is augmented by high NaCl intake.