bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Ethanol on Sleep and Central Respiratory Motor Activity
Authors: Vecchio Laura Marie , Liu Hattie , Harding Stephen , Le Anh , Horner Richard 
Published: June 2021

Ethanol worsens sleep‐disordered breathing in humans. To determine whether this effect may be due to a central depression of respiratory motor activity and/or sedation, we recorded sleep‐wake states, genioglossus and diaphragm muscle activities in freely‐behaving rats (n=10), following intra‐peritoneal injection of 1.25 g/kg ethanol or saline (control) in random order. Ethanol injections resulted in maximum blood levels of 140 mg/dl, i.e., a physiologically relevant level for producing impairment of cognitive and motor behavior in rats and humans. Ethanol decreased wakefulness (P=0.03), increased non‐rapid eye movement (NREM) sleep (P=0.02) but had no effect on REM sleep (P=0.81). Ethanol also decreased respiratory‐related genioglossus activity in wakefulness (P=0.02), but not diaphragm amplitude or respiratory rate in any state. However, application of ethanol in doses ranging from 0.025 to 1 M directly to the hypoglossal motor nucleus in isoflurane‐anesthetised rats (n=10) did not suppress genioglossus muscle activity. In conclusion, ethanol at physiologically relevant concentrations promoted sleep indicative of a sedating effect. The lack of effect on genioglossus muscle activity with ethanol applied directly to the hypoglossal motor nucleus suggests that the suppression observed with systemic administration was mediated via effects operating outside this motor pool.Supported by: CIHR
Collecting duct‐specific Rh C Glycoprotein deletion alters basal and acidosis‐stimulated renal ammonia metabolism
Authors: Lee Hyun‐Wook , Verlander Jill W. , Bishop Jesse , Igarashi Peter , Handlogten Mary E. , Weiner I. David 
Published: June 2021

Renal collecting duct NH3 secretion is a key element of acid‐base regulation and has been attributed to passive diffusion. Mammalian Rh Glycoproteins are similar to Mep/Amt ammonia transporters in other organisms.[jvr1] Rh C Glycoprotein (Rhcg) is expressed in the collecting duct. To determine if the collecting duct secretes NH3 via Rhcg, we generated mice with collecting duct‐specific Rhcg deletion (KO), which we confirmed by immunohistochemistry. KO mice had loxP sites in introns 4 and 9 of the Rhcg gene (Rhcgfl/fl) and expressed Cre‐recombinase under control of the Ksp‐cadherin promoter (Ksp‐Cre). Control (C) mice were Rhcgfl/fl but Ksp‐Cre‐negative. Basal urinary ammonia excretion was less in KO vs C mice (71±9 vs 94±6 μmol d−1, n=8 and 6, p<0.05). In mice acid‐loaded by adding 0.4M HCl to normal rodent chow, day 1 urinary ammonia excretion did not change significantly in KO mice (Δ=‐16±19 μmol d−1, n=6, p=NS), whereas it increased significantly in C mice (Δ=154±37 μmol d−1, n=6, p<0.005). Urinary ammonia excretion was significantly less in KO vs C mice each subsequent day. After 7 days, metabolic acidosis, measured as serum [HCO3−], was more severe in KO than C mice (16.2±1.0 vs 20.5±0.8 mmol/L, p<0.02, n=6 and 5). Other differences between acid‐loaded KO and C mice included lower urine pH at day 2 and decreased glutamine synthetase and increased PEPCK and Rhbg expression at day 7 in KO mice. We conclude: 1) collecting duct ammonia secretion is, at least in part, mediated by Rhcg and not due solely to passive NH3 diffusion; and 2) during metabolic acidosis compensatory responses to Rhcg deletion contribute to partial increases in ammonia excretion.This work was supported by NIDDK.
Regulation of sympathetic nerve activity and arterial pressure by the rostral ventrolateral medulla in obese Zucker rats.
Authors: Huber Domitila Augusta , Schreihofer Ann Marie 
Published: June 2021

Adult obese Zucker rats (OZR) have elevated sympathetic nerve activity (SNA) and arterial pressure (AP) with exaggerated sympatho‐excitatory responses (somatic and diving reflex) compared to lean Zucker rats (LZR). The present study sought to determine whether the altered control of SNA and AP in OZR could be due to enhanced glutamatergic or reduced GABAergic control of the rostral ventrolateral medulla (RVLM). Adult rats (14‐17 wks) were anesthetized with urethane (1.5 g/kg, iv), ventilated, and paralyzed for recording of SNA and AP. Microinjections of glutamate (1 nmol/100 nl) were performed into the RVLM to locate sites for maximal increases in SNA and AP (1.4 ‐ 1.8 mm rostral to calamus, 1.7 ‐ 2.1 mm lateral to midline, 2.7 ‐ 3.1 mm ventral; tip angled 20° rostrally). Baseline mean AP of OZR was significantly higher than LZR (n=6, 124 ± 2 mmHg in OZR vs n=6, 108 ± 6 mmHg in LZR, P<0.05). The OZR had larger maximal increases in AP (n=6, 30 ± 3 mmHg in OZR vs n=6, 20 ± 2 mmHg in LZR, P<0.05) and SNA (n=6, 74 ± 8 % of baseline in OZR vs n=6, 58 ± 8 % in LZR) than LZR. After the blockade of GABAA receptors in the RVLM (gabazine; 100 pmol/100nl) the increases in AP (n=6, 58 ± 11 mmHg in OZR vs n=6, 42 ± 7 mmHg in LZR) and SNA (n=6, 83 ± 17 % of baseline in OZR vs n=6, 84 ± 21 % in LZR) were similar between groups. These results suggest that the RVLM is more easily activated by glutamate, but that tonic GABAergic inhibition of the RVLM is not altered in OZR compared to LZR.Grant Support: NIH R01HL086759
Chronic Aortic Barodenervation switches salt‐sensitive normotension to salt‐sensitive hypertension in rats
Authors: Rodríguez‐Martínez Manuel , Rodríguez‐Pérez Adriana S. , López‐ Rodríguez Juan F. , Calvo‐Turrubiartes Miriam Z. 
Published: June 2021

Our prior (EB08 Abs.738.4) cross sectional study suggested that bilateral chronic aortic baroreceptor denervation (AD) induces salt‐sensitive normotension in rats. To assess this in depth, mean arterial pressure (MAP) was measured intra‐arterially over time (3 times) in two groups of conscious Wistar rats. The first time (PreDen) was measured in caudal artery before random sham (SH, n = 7) or real AD (n = 10); the second one was measured in left femoral artery after 7 days on low sodium diet (PostDen LNaD = 0.04% Na) and the third time was measured in right femoral artery after 21 days on high sodium diet (PostDen HNaD = 8% Na). The effectiveness of AD was judged by Box‐Cox transformation of PHE(1) and SNP (2) slope [((( [3 ‐ (HR2‐HR1/ MAP2‐MAP1)] −0.4) ‐1) / ‐0.046)] obtained in conscious state. Salt Sensitivity = SS = (PostDen HNaD MAP ‐ PostDen LNaD MAP, mmHg). Delta of MAP (PostDen MAP ‐ PreDen MAP, mmHg) on both LNaD and HNaD were calculated too. &p = 0.05, *p <0.003 vs SH and + p < 0.01, # p < 0.009 vs LNaD.PreDen PostDen PostDen SS Delta MAP DeltaMAPLNaD HNaD LNaD HNaDSH 105.0 114.0 122.0+ 7.7 9.0 16.7+±2.7 ±1.8 ±1.7 ±2.5 ±2.6 ±2.3AD 101.0 123.2& 134.5*# 11.3 22.2* 33.5*#±2.0 ±2.4 ±2.8 ±2.6 ±2.0 ±2.4ConclusionsWistar rats show salt‐sensitive normotension that chronic AD switches to salt‐sensitive hypertension. Supported by: CONACYT 62282
Effects of Digoxin‐binding Fab in a Rat Model of Preeclampsia
Authors: Agunanne Enoch , Horvat Darijana , Uddin Mohammad N , Puschett Jules 
Published: June 2021

ObjectiveTo investigate the effects of Digibind® (D, digoxin immune Fab, bovine) in the treatment of preeclampsia (PE) in a rat model. D inhibits the cardenolides and may have cross‐reactivity with the bufodienolides.MethodsWe induced PE in rats by administering DOCA and replacing their drinking water with 0.9% saline. D (10mg/kg) was given intraperitoneally on days 10‐21 of pregnancy (PDS‐D rats, n= 9). These were compared to PDS rats that received no D. (PDS, n=8) and normal pregnant rats (NP, n=10).ResultsThe mean initial blood pressure (BP) was 111 ± 2, 101 ± 3, 104 ± 2 mmHg respectively for PDS‐D, PDS, NP. There was no statistical difference between PDS and NP initial BP. The final BP was 102 ± 1, 154 ± 3, 93 ± 4 mmHg respectively for PDS‐D, PDS, NP, (p < 0.001 PDS vs. NP and PDS vs. PDS‐D). The mean 24 hour protein excretion on day 21 was 2.4 ± 0.8, 5.4 ± 1.0, 2.3 ± 1.2 mg/24 hours, respectively for PDS‐D, PDS, NP, (p< 0.001 PDS‐D vs. PDS). The mean number of pups/litter was 12.8 ± 2.8, 11.5 ± 1.2, 14.9 ± 1.9 respectively for PDS‐D, PDS, NP (p < 0.05 PDS‐D vs. NP). Also, about 30% of the PDS‐D pups showed developmental retardation, compared to the NP indicating intrauterine growth restriction (IUGR).ConclusionsD produced significant lowering of the blood pressure and proteinuria in a rat model of PE. However, teratogenic effects and IUGR were also observed in the PDS‐D group.Scott, Sherwood/Brindley Foundation
DOCA‐salt hypertensive rats display decreased vascular reactivity to urotensin‐II
Authors: Carneiro Fernando Silva , Carneiro Zidonia Nunes , Giachini Fernanda Regina Casagrande , Lima Victor V , Webb R Clinton , Tostes Rita C 
Published: June 2021

IntroductionUrotensin‐II (U‐II) is a vasoconstrictor peptide and its potency can be up to 100 fold greater than that of endothelin‐1 (ET‐1). ET‐1 plays a major role in the vascular changes associated with salt‐sensitive hypertension, but the effects of U‐II in arteries from these animals have not yet been defined.ObjectiveWe hypothesized that DOCA‐salt rats have increased vascular reactivity to U‐II.Methods and ResultsWistar rats were unilaterally nephrectomyzed and deoxycorticosterone‐acetate (DOCA) (200mg/Kg) pellets were implanted. DOCA rats received water containing 1% NaCl/0.2% KCl, for 5 weeks. Aortic rings were mounted in myograph chambers and functional studies were performed. DOCA rats displayed increased systolic pressure (Control: 117±1 vs DOCA: 179±3; mmHg). Maximal contractions (mN) to U‐II were decreased in endothelium‐intact (Control: 16.6±1 vs DOCA: 8.8±1) and endothelium‐denuded (Control: 21.3±1.1 vs DOCA: 10.4±0.9) aortas from DOCA rats. This difference was abolished in endothelium‐intact vessels incubated with 10−5M urantide (U‐II antagonist) (Control: 13.5±0.9 vs DOCA: 12.7±0.9).ConclusionOur results suggest that U‐II production/release is augmented in mineralocorticoid hypertension and that decreased vascular reactivity to the peptide may represent counter‐regulatory mechanisms that limit additional vascular damage to this potent vasoconstrictor.
Upregulated TRPC3 expression and function in vascular smooth muscle during hypertension
Authors: Noorani Muzamil M.Z. , Chen Jie , Marrelli Sean P. 
Published: June 2021

TRPC3 has been demonstrated to play a role in regulating arterial tone through smooth muscle cell (SMC) depolarization. Recent studies indicate that TRPC3 expression is upregulated in pulmonary artery SMC in idiopathic pulmonary hypertension. We sought to determine if TRPC3 was upregulated in the systemic circulation during hypertension, and if so, whether this upregulation renders arteries more contractile to physiological agonists.Protein was extracted from carotid arteries (CA) of male SHR and WKY rats. Western blot analysis demonstrated 3.1 ± 1.2 times greater TRPC3 expression in SHR versus WKY. Next, TRPC3 function was evaluated in freshly isolated CA SMC by whole cell patch clamp; TRPC3 currents were elicited by extracellular application of uridine triphosphate (UTP; 60 µM). UTP‐stimulated currents were greater in SHR compared with WKY or previous studies with normotensive Long‐Evans rats. Peak UTP‐stimulated inward currents (at ‐110 mV) were ‐36, ‐18, and ‐23 pA, respectively.In summary, we have demonstrated upregulated TRPC3 expression and function in CA during hypertension. Future planned studies will evaluate CA responses to contractile agonists. Supported by: AHA 0665100Y and NIH HL088435 (SPM)
Obligatory role for phosphatidylinositol 4, 5‐bisphosphate (PIP2) in activating native TRPC store‐operated channels (SOCs) in vascular myocytes
Authors: Saleh Sohag , Ju Min , Albert Anthony , Large William 
Published: June 2021

We have previously shown that protein kinase C (PKC) has a pivotal role in activating diverse TRPC SOCs in vascular myocytes (Albert & Large, 2002; Saleh et al, 2008). The present work investigated mechanisms involved in linking PKC activity with gating of SOCs and provides evidence that PIP2 is an obligatory molecule in this process.Bath application of PIP2 to quiescent inside‐out patches from rabbit portal vein myocytes activated SOC activity, which was inhibited by anti‐TRPC1 antibodies (Albert & Large, 2003; Saleh et al, 2008). Cyclopiazonic acid (CPA)‐, BAPTA‐AM‐ and phorbol esters (PDBu)‐induced SOC activity was inhibited by an anti‐PIP2 antibody and by pre‐treatment with agents that deplete tissue PIP2 levels. Pre‐treatment with PDBu and the PKC inhibitor, chelerythrine, enhanced and decreased SOC stimulation by PIP2. Co‐immunoprecipiation experiments showed association between PIP2 and TRPC1 at rest and moreover that PKC‐dependent phosphorylation of TRPC1 was increased by CPA and PDBu and decreased by chelerythrine.These data clearly indicate that PIP2 activates SOCs and that PIP2 is obligatory for stimulation of SOCs via PKC‐dependent phosphorylation of TRPC1.Albert & Large (2002) J Physiol 544 113‐25; Saleh et al (2008) J Physiol 566 2463‐76
Cardiovascular effects of noradrenaline injected into the Medial Nucleus of Amígdala (MeA) of unanesthetized rats.
Authors: Fortaleza Eduardo Trindade , Scopinho América Augusto , Correa Fernando Morgan Aguiar 
Published: June 2021

IntroductionThe MeA, is involved with physiological and behavioral processes modulation, as well as regulation of the autonomic nervous system. Some evidences indicating that electrical rats MeA stimulation is able to evoke cardiovascular response. The noradrenaline (NA) is a neurotransmitter involved in the control of cardiovascular responses into the several structures in the central nervous system. The MeA received noradrenergic innervations of the A6 neurons and locus coeruleus (LC). Moreover, binding studies demonstrate noradrenergic receptors in this area.ObjectiveThe aim of the present work is characterize the cardiovascular responses evoked by local administration of NA in the MeA.Methods and ResultsMale Wistar rats were used. Cannulaes was implanted in the MeA using a stereotaxic apparatus. A catheter was implanted into the femoral artery for blood pressure and heart rate (HR) recording. Injecting different doses of NA (3, 9, 27 or 45 nmol/100 nL) into the MeA of normotensive rats (baseline MAP=100±2 mmHg and HR=369 ± 4bpm, n=25) caused dose‐related pressor responses and HR decrease. Nonlinear regression analysis indicated a significant correlation between doses and cardiovascular responses.ConclusionOur results reinforce the idea that noradrenergic mechanisms into the MeA are involved in cardiovascular control.Financial SupportsFAPESP, CNPQ and FAEPA.
Reverse Respiratory Sinus Arrhythmia and Baroreceptor Sensitivity in Amyotropic lateral Sclerosis
Authors: Bartels Matthew N , De Meersman Ronald E , Atkeson Amy , Downey John A , Basner Robert C 
Published: June 2021

Respiratory sinus arrhythmia (RSA) is heart rate variability in synchrony with normal respiration, by which the R‐R interval on an electrocardiogram (EKG) is shortened during inspiration and prolonged during expiration. During a normal respiratory cycle intrathoracic pressure (ITP) decreases and increases during inhalation and exhalation, respectively. These pressure changes stimulate baroreceptors (BRS).AIMSWe studied baroreceptor responses during continuous positive airway pressure (CPAP), in which ITPs are reversed compared to normal breathing. In addition, we compared the BRS responses during CPAP between amyotropic lateral sclerosis patients (ALS) and normal subjects.MethodsRespiration, EKG, and beat‐to‐beat blood pressures were collected during CPAP and sham treatments. Baroreceptor analysis was derived using the transfer function between blood pressure and R‐R interval changes. Analysis of variance was used to determine statistical differences at an a‐level of P < .05.ResultsPreliminary trends in BRS were seen between the groups (ALS < 3±.02 mmHg/sec vs normals > 6±2.2 mmHg/sec).DiscussionPreliminary results suggest that BRS is maintained during CPAP but appears to trend toward differences in magnitude between ALS patients and normals. VIDDA foundation.
Sex differences in the balance of sympathetic activity, peripheral resistance and cardiac output: implications for blood pressure control
Authors: Hart Emma C , Charkoudian Nisha , Joyner Michael J , Curry Timothy B , Eisenach John H , Wallin Gunnar 
Published: June 2021

The sensitivity of the baroreflex control of muscle sympathetic nerve activity (MSNA) represents the responsiveness of MSNA to changes in blood pressure, whereas the baroreflex threshold diagram evaluates the likelihood of a burst occurrence over a range of resting blood pressure values. We hypothesized that the slope of the threshold diagram would show a significant positive correlation with sympathetic baroreflex sensitivity (BRS). We compared BRS calculated by the Modified Oxford technique (ModOx) with the slope and midpoint (T50) values from threshold analysis (threshold) in 10 participants (9M, age 26 yrs ± 3[mean ± SEM]). MSNA (peroneal microneurography) and blood pressure (brachial catheter) were measured at rest and during vasoactive drug boluses (ModOx). A threshold diagram was created for each subject during rest by associating DBP to the % occurrence of a burst over a 4 min period prior to the ModOx drugs. The midpoint (T50) of this diagram was defined as the DBP at which 50% of the diastoles were associated with a burst. ModOx‐derived BRS positively correlated with the slope of the threshold diagram (r = 0.64, P<0.05), but not with the T50 (r =0.11, P > 0.2). Our results suggest that the slope of the threshold diagram may be a better index of ModOx‐derived BRS values compared to more commonly used "spontaneous" baroreflex techniques.NIH HL‐083947
Age dependent effects of haemorrhage on the arterial baroreflex control of heart rate in conscious lambs
Authors: Samhan Mohamed A , Qi Wei , Smith Francine G 
Published: June 2021

Previously, we showed that arterial pressure decreased after moderate haemorrhage in conscious lambs, whereas a compensatory increase in heart rate occurred only in newborns. These findings provided evidence to suggest an age‐dependent effect of haemorrhage on the arterial baroreflex control of heart rate. Therefore, in the present study, the arterial baroreflex was assessed in conscious lambs aged 14±1 days (G I, N=4) and 43±7 days (G II, N=6) before (control, C) and at 30 and 60 min after haemorrhage (30% of calculated blood volume). The following parameters governing the arterial baroreflex were evaluated: Heart rate range (P1), slope coefficient (P2), systolic arterial pressure at midpoint (P3), minimum HR (P4), and maximum gain (Gmax). Values are mean±SEM; *p<0.05 compared with C; †p<0.05 compared with G I.Predominant effects of haemorrhage were: a decrease in P1 which was greater in G I than G II, and a decrease in Gmax which was greater in G II than G I. Therefore, severe haemorrhage alters several parameters governing the arterial baroreflex control of heart rate, these effects being developmentally regulated.This research was supported by the Canadian Institutes of Health Research (CIHR).
The medial nucleus of amygdala (MeA) mediate the cardiovascular responses evoked by noradrenaline microinjected into the lateral septal area (LSA) in rats
Authors: Scopinho América Augusto , Fortaleza Eduardo Albino Trindade , Correa Fernando Morgan Aguiar 
Published: June 2021

IntroductionWe demonstrated that the microinjection of noradrenaline into the LSA evoked pressor and bradycardic responses mediated by vasopressin release. Moreover, the microinjection of cobalt or selective non‐NMDA antagonist NBQX into the paraventricular nucleus (PVN) blocked the pressor response and bradycardia evoked by NA injected into the LSA, suggesting the PVN as the final structure in this pathway. Anatomical dates demonstrated that no direct connections were observed between the LSA and the PVN or the SON. The MeA is a structure involved in cardiovascular control. Projections from the LS to the MeA have also been described in the literature and MeA sends projections to PVN.ObjectiveTo investigate if MeA acute ablation by the injection of cobalt blocked the cardiovascular responses to NA microinjection into the LSA.Methods and ResultsMale Wistar rats were used. Cannulaes was implanted in the LSA and the ipsilaterally in the MeA using a stereotaxic apparatus A catheter was implanted into the femoral artery for blood pressure and heart rate recording. The microinjection of cobalt into the MeA blocked the pressor and bradycardiac responses evoked by NA microinjection into the LSA.ConclusionOur results suggest that synapses in the MeA are involved in the mediation of the pressor and bradycardiac response to the microinjection of NA into the LSA.Financial SupportCAPES and FAEPA.
Intracerebroventricular (ICV) injections of nesfatin‐1 induces c‐fos expression in the rat forebrain.
Authors: Martin Theodore J. , Moreau Jason M. , Ajani Abdallah A. , Oiamo Tor H. , Maximos Mira , Ciriello John 
Published: June 2021

The forebrain contains neuronal circuits of critical importance in the regulation of food intake. Nesfatin has been identified as a satiety peptide within central neurons. ICV injection of nesfatin‐1 decreases food intake in a dose‐dependent manner and result in a decrease in body weight. However, the central pathways activated by nesfatin‐1 are not known. In this study, the distribution of neurons expressing fos‐like immunoreactivity following ICV infusions of nesfatin‐1 (5 pmol/µl; 2 µl followed by two 1 µl injections every 30 min) was identified in the rat forebrain. Fos labeled neurons were found within the hypothalamus: paraventricular, supraoptic, arcuate, lateral, dorsomedial and posterior nuclei. In addition, the organum vasculosum of the lamina terminalis, median preoptic nucleus and subfornical organ expressed fos labeling. Finally, fos labeling was observed within the midline thalamic nuclei, lateral septum, islands of Calleja, medial preoptic nucleus and medial and central nuclei of amygdala. These data suggest that nesfatin‐1 exerts its anorexigenic effects through the activation of forebrain structures previously implicated in the regulation of food intake and energy expenditure.Supported by Heart and Stroke Foundation of Ontario.
Prenatal hypoxia programs an altered β1/β2 adrenoceptor subtype ratio in the heart of adult broiler chickens
Authors: Lindgren Isa , Carreras Badosa Gemma , Altimiras Jordi 
Published: June 2021

Background and purposeβ‐adrenoceptors (βARs) are essential for cardiac regulation. Adverse events in fetal life may program the adult phenotype for cardiovascular disease. Previous studies from our lab show that chronic prenatal hypoxia renders an adult animal with decreased sensitivity to cardiac βAR stimulation. To investigate whether low fetal oxygen conditions have a programming effect on the β1/β2AR ratio in the adult, causing the previously shown decrease in adult βAR sensitivity.Method and resultsWe studied total β‐AR density (Bmax) and the ratio of β1/β2 subtypes in the broiler chicken heart (14 and 35 days post hatching, P14 and P35) prenatally developed in normoxia (21% O2, N) or chronic hypoxia (14% O2, H). To obtain total Bmax we incubated ventricular tissue with the tritiated β‐antagonist [3H]CGP‐12177. The β1/β2 ratio was obtained by specific inhibition of β1 by CGP‐20712A and β2 by ICI‐11855 in the presence of 2nM of [3H]CGP‐12177. Total Bmax did not differ between treatments in either P14 or P35, but βAR density decreased with age. There was significantly more β2 than β1 in P35H, while P35N showed a 50/50 ratio of the two subtypes.ConclusionPrenatal hypoxia programs an altered βAR subtype ratio in the adult in favor of β2 which may be the cause of the previously observed decrease in βAR sensitivity.Supported by FORMAS (Dnr. 2004‐1331).