bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cold Pressor Test: Medullo‐Spinal Pathways and Neurotransmitters
Authors: Nakamura Takeshi , Sapru Hreday N 
Published: June 2021

The neural pathways and transmitters that mediate pressor and tachycardic responses to the cold pressor test are not firmly established. The present experiments were designed to delineate these pathways. Experiments were carried out on urethane‐anesthetized, artificially ventilated, barodenervated, male, Wistar rats. The rats were fixed in a stereotaxic instrument and placed in a plexiglass rectangular dish. Ice‐cold water was rapidly poured into the dish to immerse the ventral half of the rat's body and then removed by rapid suction. Cold water immersion for 2 min elicited an increase in mean arterial pressure (40–46 mmHg) and heart rate (60–76 bpm). Bilateral vagotomy had no significant effect on the pressor responses but significantly reduced the tachycardic responses. Bilateral blockade of ionotropic glutamate receptors (IGLURs), by injections of D‐AP7 and NBQX, in the rostral ventrolateral medullary pressor area (RVLM) or the spinal cord significantly decreased the pressor responses. HR responses remaining after the blockade of IGLURs in the spinal cord were abolished after bilateral vagotomy. These results indicate that: 1) the pressor and tachycardic responses to cold pressor test are mediated by ionotropic glutamate receptors in the RVLM and the spinal cord, and 2) inhibition of the vagal input to the heart also contributes to the tachycardic responses.Support: NIH grants HL 024347 and HL076248.
Microinjections of alpha‐MSH into the nucleus ambiguus of the rat elicit vagally mediated bradycardia
Authors: Chitravanshi Vineet C , Sapru Hreday N 
Published: June 2021

Alpha melanocyte stimulating hormone (alpha‐MSH) is one of the pro‐opiomelanocortin‐related end products. Alpha‐MSH containing neurons are found in different hypothalamic nuclei and the nucleus tractus solitarius. Since these brain regions are known to project to the nucleus ambiguus (NA), it was hypothesized that alpha‐MSH may elicit cardiac effects in the NA. Experiments were done on urethane‐anesthetized, artificially ventilated, adult, male, Wistar rats. NA was identified by microinjections (30 nl) of L‐glutamate; bradycardic responses with no changes in blood pressure (BP) were elicited. Unilateral microinjections (30 nl) of different concentrations (0.1–1.6 mM) of alpha‐MSH into the NA elicited bradycardic responses (7–44 beats/min) with no changes in BP. The bradycardic responses to maximally effective concentration of alpha‐MSH (0.8 mM) lasted for 10 min and were blocked by prior microinjections of a specific MC4 receptor antagonist. MC4 receptor antagonist by itself elicited a small decrease in heart rate. Bilateral vagotomy abolished the bradycardic responses to microinjections of alpha‐MSH into the NA. These results indicate that: 1) microinjections of alpha‐MSH into the NA elicit bradycardia, 2) the bradycardia is vagally mediated, 3) MC4 receptors mediate these actions, and 4) the melanocortin input to the NA may be tonically active.Support: NIH grants HL024347 and HL076248.
Increases and Decreases in Arterial Pressure Result in the Activation of Phenotypically Different Populations of Neurons in the Nucleus of the Solitary Tract (NTS)
Authors: Austgen James R , Friskey Sarah A , Heesch Cheryl M , Hasser Eileen M 
Published: June 2021

The NTS is the termination site of multiple visceral afferents, including the arterial baroreceptors. As expected, increasing blood pressure (BP) activates second order baroreflex neurons in the NTS. However, decreasing BP also activates NTS neurons. We hypothesized that different phenotypes of neurons are activated by increases vs. decreases in BP. Male Sprague‐Dawley rats, instrumented with arterial and venous catheters, received microinjections of the retrograde tracer Fluoro‐Gold (FG) into the caudal ventrolateral medulla. After 5d, animals were administered (i.v.) saline, phenylephrine (PE: 15 mg/kg/min), or diazoxide (DZ: 50 mg/kg, supplement 12.5 mg/kg) and monitored for 90 min. Rats were perfused, brains cut into 30 μm coronal sections, and sections immunohistochemically treated for Fos and neuronal nitric oxide synthase (nNOS) or tyrosine hydroxylase (TH). Fos expression was significantly enhanced by increases (PE, 201 ± 39) and decreases (DZ, 206 ± 41) in BP compared to saline (18 ± 6). Increased BP resulted in significantly greater activation of FG (consistent with baroreflex activation) and nNOS containing neurons compared to saline. In contrast, decreases in BP resulted in significantly greater activation of TH containing neurons compared to saline. Thus, phenotypically separate populations of NTS neurons are activated by increases vs. decreases in BP.AHA #0710005Z (JRA); HL54669 (EMH)
Low doses of corticosterone act in the dorsal hindbrain to enhance the arterial pressure response to both acute and repeated stress
Authors: Looney Benjamin M , Daubert Daisy L , Su Ye , Scheuer Deborah A 
Published: June 2021

We have shown that chronic treatment of the dorsal hindbrain (DHB) with 100% corticosterone (Cort) pellets enhances the mean arterial pressure (MAP) response to acute stress. The current experiments were performed to determine the effect of lower doses of Cort on the arterial pressure and heart rate responses to acute and repeated stress. Experiments were performed on male Sprague‐Dawley rats implanted with DHB Sham, 10%, 50% or 100% Cort pellets, n=4–6 per group. MAP and heart rate were measured via radiotelemetry (Data Science International). Rats were subjected to 1 h of restraint stress on days 6, 13, 14 and 15 days post pellet implantation. All doses of Cort significantly enhanced (P<0.05) the integrated MAP response to both acute and repeated stress relative to sham treatment. For example, on day 6 DHB sham, 10, 50 and 100% Cort treatment increased arterial pressure by 1509±496, 2736±193, 2737±499 and 2471±412 mmHg/60 min respectively, and on day 14 by 1959±328, 2952±414, 2435±301 and 2612±301 mmHg/60 min respectively. There were no significant differences (P=0.08) in baseline MAP between groups, but the 10% dose increased MAP from 103±3 on day 6 to 109±4 mmHg on day 15 (P<0.05). There were no significant effects of DHB treatment on baseline HR or the integrated HR response to stress. We conclude that even low doses of Cort enhance the arterial pressure response to acute and chronic stress.Funded by NIH grant # HL 076807.
AQP1 and AQP4 gene polymorphisms and endurance performance status in hispanics
Authors: Matos Carla , Nieves Juan J , Castro Paola , Morgado Andres , Salgado Jeanette , Martinez Juan L , Lopez‐Taylor Juan , Rivera Miguel A 
Published: June 2021

Associations between single nucleotide polymorphisms (SNPs) in the AQP1 and AQP4 genes with endurance performance status were recently reported (MSSE 37(5):S164, 2005 and MSSE 39(5):S279, 2007, respectively). This study attempted to characterize the association between the AQP1 and AQP4 genes SNPs and endurance performance status in Hispanics. In a case‐control study, genomic DNA was successfully genotyped from 460 Hispanic subjects. Cases (n = 115) were long distance runners finishers in the highest 3 percentile, by age and gender, during their participation in an international marathon (42 km) race, while healthy controls (n=168) were those in the lowest 3 percentile for their respective age and gender. Controls (n = 64) were subjects with severely compromised cardiorespiratory functions. The AQP1 and AQP4 genes SNPs were detected by the tetra‐primer ARMS‐PCR procedure. Genotypes were determined by PCR product size. The observed allelic and genotypic frequencies were compared by endurance performance status using Chi‐square test statistic. The three expected AQP1 and AQP4 genotypes were observed in each of the three groups. No significant (P>0.05) associations were observed between genotypes or SNPs carrier status and endurance performance classification. CONCLUSIONS: We found no support for the hypothesis of association between the AQP1 and AQP4 genes SNPs and endurance performance status in Hispanics.Supported by CRC‐RCMI UPR‐MSC Grant #1P20RR11126, RCMI Basic Sciences #G12RR03051.
Highly Ca2+ ‐selective TRPM channels regulate IP3‐dependent oscillatory Ca2+ signaling in the C. elegans intestine
Authors: Xing Juan , Yan Xiaohui , Estevez Ana , Strange Kevin 
Published: June 2021

Posterior body wall muscle contraction (pBoc) in C. elegans occurs rhythmically and mediates defecation. pBoc is controlled by IP3‐dependent Ca2+ oscillations in the intestine. The intestinal epithelium can be studied by patch clamp electrophysiology, Ca2+ imaging, reverse/forward genetics analysis, molecular biology and thus provides a powerful model to develop an integrated understanding of a non‐excitable cell oscillatory Ca2+ signaling pathway. Intestinal cells express a TRPM‐like outwardly rectifying Ca2+ (ORCa) current. Two TRPM homologs, GON‐2 and GTL‐1, are expressed in the intestine. Using deletion and severe loss‐of‐function alleles of the gtl‐1 and gon‐2 genes, we demonstrate that GON‐2 and GTL‐1 are both required for maintaining rhythmic pBoc and intestinal Ca2+ oscillations. Loss of GTL‐1 and GON‐2 function inhibits IORCa ∼70% and ∼90%, respectively. IORCa is undetectable in gon‐2; gtl‐1 double mutant cells. Our results demonstrate that 1) both gon‐2 and gtl‐1 are required for ORCa channel function, and 2) GON‐2 and GTL‐1 function interdependently to mediate IORCa. Epistasis analysis suggests that GON‐2 and GTL‐1 function in the IP3 signaling pathway to regulate intestinal Ca2+ oscillations. We postulate that GON‐2 and GTL‐1 form heteromeric ORCa channels and function to regulate IP3 receptor activity and possibly to refill ER Ca2+ stores.Source of research support: NIH R01 grant GM74229
Diameter and Compliance of the greater Saphenous Vein‐The Effect of Age and Glyceryl Trinitrates.
Authors: Zachrisson Helene , Lindenberger Marcus , Länne Toste 
Published: June 2021

OBJECTIVES: The greater saphenous vein (GSV) is commonly used in autologous vein graft surgery in the lower limb. GSV diameter (D) has proven to influence graft patency and venous compliance (C) might be of importance. The aim of the study was to evaluate the effect of age on GSV D and C, and the effect of glyceryl trinitrate (GTN).METHODS : The D and C of the GSV, with and without GTN, were examined with B‐mode ultrasound in 14 young (YM, 25±1 y) and 12 old (OM, 70±2 y) males. The GSV D was measured at rest, and after 6 min of venous stasis (60 mmHg). Pressure‐diameter curves during a linear venous pressure decrease were produced. C with was calculated using the quadratic regression equation (?diameter) = β0 + β1·(cuff pressure) + β2·(cuff pressure)2RESULTS: The GSV D at rest was 3.7±0,2 mm and 2.8±0.2 mm in YM and OM respectively, P<0.01. Venous congestion increased GSV D significantly in YM and OM respectively, (P<0.001). Mean GSV C (β1) was 0,017±0.0035 and 0.0085±0,0039 in YM and OM respectively, (P=0.1). GTN increased resting D by 13% in OM , (P<0.01), but not in YM. After GTN, compliance was significant greater in YM, (p<0.05).CONCLUSIONS: The diameter, and compliance of the GSV decreases with age, indicating defective venous wall function. The effect of venous compliance on graft patency deserves further study.
14,15‐Epoxyeicosatrienoic acid increases endothelial permeability via TRPV4 and KCa channel activation in mouse lung
Authors: Jian Ming‐Yuan , Liedtke Wolfgang , Townsley Mary I. 
Published: June 2021

We have shown that the increased permeability response to 14,15‐epoxyeicosatrienoic acid (EET) in rat lung requires Ca2+ entry via the vanilloid transient receptor potential channel TRPV4. The current study tested the hypothesis that the permeability response to 14,15‐EET requires both TRPV4 and Ca2+‐activated K+ channels(KCa). In lungs isolated from anesthetized TRPV4+/+ (WT) and TRPV4−/− (KO) mice, endothelial permeability was measured via the filtration coefficient (Kf) at baseline and after treatment with 14,15‐EET (3 μM). Baseline Kf was no different in WT and KO groups (0.011±0.001 vs 0.010±0.001 ml/min/cmH2O/g dry wt, mean±SEM). In WT lungs perfused with physiological buffer (n=6), 14,15‐EET increased Kf 2.9‐fold (p<0.001), a response blocked in lungs pretreated with the TRPV antagonist ruthenium red (3 μM, n=5), and absent in KO lungs (n=5). The permeability response to 14,15‐EET in WT lungs was attenuated in low Ca2+ (0.02 mM) but returned with Ca2+ addback (2.2 mM), in the absence (n=4) or presence of iberiotoxin (100 nM, n=4). Permeability did not increase with Ca2+ addback in groups treated with ruthenium red (n=4), the combination (n=4) of charybdotoxin (100 nM)/apamin (300 nM) or apamin alone (n=3). We conclude that intermediate (IK) and/or small (SK) conductance KCa channels contribute to the TRPV4‐mediated Ca2+ entry‐dependent endothelial permeability response to 14,15‐EET.Supported by HL066299.
Increased AQP2 and AQP3 expression in renal cortex in COX‐2 deficient mice
Authors: Norregaard Rikke , Topcu Sukru Oguzkan , Madsen Kirsten , Nielsen Soren , Jensen Boye L. , Frokiaer Jorgen 
Published: June 2021

Previously we demonstrated that COX‐2 activity contributes to downregulation of aquaporin‐2 (AQP2) in rats subjected to 24h of bilateral ureteral obstruction (BUO). In this study we hypothesized that COX‐2 exerts tonic suppression of renal AQPs. We investigated the expression of AQPs and cyclooxygenase‐1 (COX‐1) in cortex (COR) and inner medulla (IM) tissue from COX‐2−/− mice. Kidneys from 4 week old COX‐2−/− (C57Bl6, 1. generation) mice and wild type (WT) littermates were prepared for semiquantitative immunoblotting. A subset of mice was perfusion fixed for immunohistochemistry (IHC). Plasma creatinine, osmolality and urea levels were increased in the COX‐2−/− mice compared to the WT. COX‐2 protein was not detectable in COX‐2−/− kidneys. COX‐1 abundance was increased in both COR and IM in COX‐2 KO mice compared to the WT. This was confirmed by IHC showing labeling of collecting ducts. AQP1 expression was unchanged in COR. AQP2 protein level was increased in COR of COX‐2−/− compared to WT but was not different in IM. The expression of AQP3 was increased in COR of COX‐2−/− mice and IHC showed intense labeling of the basolateral membranes of the cortical collecting ducts in the KO mice.The data indicate that COX‐2 is involved in regulation of the expression of AQP2 and AQP3. Further studies are required but our preliminary results indicate that COX‐2 may contribute to segmental regulation of water reabsorption.
Inhalation of Dry, Normobaric Hypoxic Air Impairs Thermal Conditioning of Nasal Air in Humans: Potential Role of Nitric Oxide
Authors: Peebles Evan Richard , Roberts MF , Giraud GD , Holden WE 
Published: June 2021

Hypoxic, dry, cold air is a stress to nasal air temperature conditioning (NATC) at high altitude, where humans often complain of nasal irritation. The vasodilator nitric oxide (NO) may modulate NATC (J Appl Physiol 87:1260, 1999). Hypoxic, dry (but not cold) air also reduces NO release into nasal air (Resp Physiol 114:285, 1998). Thus, we asked if simulated high altitude (normobaric hypoxic, dry air) would impair NATC. We infused (12 L/min) normobaric, hypoxic (100% N2), dry (0% humidity) air (21° C) or dry air (21° C, 21% O2, balance N2) into the nasal passages of seven adult humans. During breath holding, air entered the nose, passed around the soft palate, exited from the mouth and was collected for analysis of nasal NO release by chemiluminescence. NO output (nL/min) was calculated as the product of NO concentration and flow rate (timed collection measured in a Tissot gasometer). Nasal air temperatures were measured at one cm intervals from the nasal verge to a depth of 7 cm by thermocouples. Exponential curve fitting generated a half‐point value—the depth where nasal air reached half the difference between ambient and maximum cavity temperature. Half point depth increased during normobaric hypoxic, dry air infusion compared with dry air indicating impediment of NATC (see table). Nitric oxide release decreased during normobaric hypoxic, dry air infusion compared with compressed air. We confirm that nasal NO release is impaired by hypoxic, dry air and further suggest that, hypoxic air impedes NATC. Our findings are consistent with a role of NO in NATC and may help explain nasal irritation in humans at high altitude.NO output (nL/min)Half‐point (cm)(Supported by the Murdock Foundation).
Modulation of BK channel expression in mouse carotid body
Authors: Lieu TinaMarie , Fujii Koichi , Sham James S.K. , Shirahata Machiko 
Published: June 2021

The carotid body (CB) is a major arterial chemoreceptor that senses low arterial PO2. Inhibition of large conductance calcium‐activated K+ (BK) channels have been hypothesized to be one of the initial key steps in hypoxic chemotransduction pathways of the glomus cell (GC). Our previous study indicates that the iberiotoxin‐sensitive BK current was more robust in GC of DBA/2J mice (high responder to hypoxia) than that of A/J mice (low responder to hypoxia). Further, glial‐derived neurotrophic factor (GDNF) appears to modulate the expression of BK channels. Since GDNF is induced by oxidative stress, we have hypothesized that oxidative stress and GDNF influences gene expression and function of BK channels, resulting in different phenotype of the GCs between the two strains of mice. We have developed a culturing system for undissociated whole CB. The carotid bifurcations with the CBs were harvested and cultured in defined media with different PO2 levels (21–95% O2) at various durations (4–24 hours). Real‐time PCR analysis revealed that GDNF levels increased in all cultured conditions tested in both strains, but the levels returned toward the control after 24 hours of culture. BKβ4 expression was similar to GDNF expression, while BKα1 and BKβ2 expression did not show consistent changes. Exposure of the DBA/2J's CB to anti‐GDNF for 12 hours decreased BKα1, β2, β4 mRNA expressions. These results are complimentary to our previous study showing that supplementation of GDNF in the A/J's CB increased functional expression of BK channels. The results further suggest that BKβ4 subunit expression may be influenced by environmental O2.Supported by HL72293 & HL 081345
An interventriculo‐septal ganglion mediates the vagal postganglionic control of contractility of the right ventricle of the cat heart
Authors: Dávila‐García Martha Isabel , Ardell Jeffrey L , Adetobi‐Oladele Elizabeth , Ekejiuba Sussan E. , Massari V. John 
Published: June 2021

We investigated the role of the interventriculo‐septal (IVS) ganglion as a potential source of vagal postganglionic control of right ventricular contractility. Prior evidence demonstrated that this ganglion provides a major source of vagal postganglionic innervation to both right and left ventricles. Blockade of the IVS ganglion with hexamethonium significantly reduced the vagally‐induced changes in right ventricular contractility in the short (transverse) and long (longitudinal) axis, without affecting heart rate or blood pressure responses to left vagal stimulation. The central pathway controlling the IVS ganglion was investigated by neuroanatomical methods. The retrograde tracer, cholera toxin‐β subunit conjugated with horseradish peroxidase (CTB‐HRP) was injected into the region of the IVS ganglion and retrogradely labeled cells were found exclusively in the ventrolateral nucleus ambiguus (NA‐VL) with the greatest concentration at the level of the area postrema. These data indicate that the IVS exerts a predominant role in modulation of RV contractile function, and that its major pre‐ganglionic input arises from the left NA‐VL.This research was supported in part by NIH‐NIGMCS 2S06GM008016 to MDG, NIH‐NINDS‐SNRP 2 U54 NS039407 to MDG and VJM, NIH‐NIMH 1 R24MH067627 to MDG and VJM, 2 G12 RR003048 from the RCMI Program to MDG and NIH‐HL71830 to JLA.
Short‐term modulation of the exercise ventilatory response is not diminished in older men
Authors: Wood Helen E. , Rowell C J , Storms C D , Klocko M N , Ranasinghe K , Mitchell G S , Babb T G 
Published: June 2021

We have previously shown that the exercise ventilatory response (EVR; defined as the slope of the relationship between ventilation and CO2 production) is reversibly augmented within a single exercise trial in the presence of added dead space (DS) in healthy young men. This augmentation arises from a mechanism known as short‐term modulation (STM; FASEB J. 21, 765.18. 2007), independent of changes in chemoreceptor (CR) feedback from rest to exercise. We hypothesized that the capacity for STM to augment the EVR with added DS is diminished in healthy older men due to age‐dependent decreases in pulmonary function and increases in EVR. Eleven men (age 69 ± 3 years) were studied at rest and during cycle exercise (10, 30, 50W; not randomized) in Control conditions (no added DS) and with added DS (200, 400, 600ml; randomized). The EVR increased sufficiently with the increasing DS volume (p<0.01), e.g. at 10W, from 33 ± 6 in Control to 47 ± 10 with 600ml DS, such that CO2 was not retained with added DS vs. Control. Hence, the increase in the EVR was not due to increased CR feedback from rest to exercise. Increasing exercise intensity diminished the EVR (p<0.01), e.g. with 400ml DS, from 40 ± 7 at 10W to 34 ± 5 at 50W; and the size of this effect varied by DS level (p<0.05). A very similar response pattern was observed in younger men. We conclude that the capacity for STM to augment the EVR with added DS is not diminished with age in healthy men.Support: The Cain Foundation, The King Foundation, and Presbyterian Hospital of Dallas
Ascorbic acid increases muscle blood flow during dynamic exercise in older healthy humans
Authors: Kirby Brett S , Voyles Wyatt F , Simpson Carrie B , Carlson Rick E , Schrage William G , Dinenno Frank A 
Published: June 2021

Age‐related increases in oxidative stress impair endothelium‐dependent vasodilation in humans, leading many to speculate that endothelial dysfunction contributes to impaired muscle blood flow and vascular control during exercise in older adults. We directly tested this hypothesis in 13 young (22±1 yrs) and 14 healthy older men and women (65±2 yrs). We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) during rhythmic handgrip exercise at 10% maximum voluntary contraction. After 5 minutes of steady‐state exercise with saline, ascorbic acid (AA) was infused via brachial artery catheter for 10 minutes during continued exercise. Prior to AA, FBF (∼28%) and FVC (∼31%) were lower in older vs young adults (P<0.05). In young adults, AA administration did not significantly influence FBF and FVC, whereas FBF and FVC increased 30±4% in older adults at end exercise (P<0.05). This increase in FBF and FVC during exercise in older adults was associated with improvements in vasodilator responses to acetylcholine (ACH; endothelium‐dependent) but not sodium nitroprusside (SNP; endothelium independent). AA had no effect on ACH or SNP responses in the young. We conclude that acute AA administration increases muscle blood flow during dynamic exercise in older adults, and this is likely due to an improvement in endothelium‐dependent vasodilation.Supported by AG‐027150