3,103 research outputs found

    Ariel - Volume 5 Number 4

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    Editors Mark Dembert J.D. Kanofskv Entertainment Editors Robert Breckenridge Joe Conti Overseas Editor Mike Sinason Photographer Scott Kastner Epistemologist Gary Kaskey Staff Ken Jaffe Bob Sklaroff Janet Weish David Jacoby Phil Nimoityn Circulation Editor Jay Amsterdam Humorist Jim Mccan

    KIR channel activation contributes to onset and steady-state exercise hyperemia in humans

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    We tested the hypothesis that activation of inwardly rectifying potassium (KIR) channels and Na+-K+-ATPase, two pathways that lead to hyperpolarization of vascular cells, contributes to both the onset and steady-state hyperemic response to exercise. We also determined whether after inhibiting these pathways nitric oxide (NO) and prostaglandins (PGs) are involved in the hyperemic response. Forearm blood flow (FBF; Doppler ultrasound) was determined during rhythmic handgrip exercise at 10% maximal voluntary contraction for 5 min in the following conditions: control [saline; trial 1 (T1)]; with combined inhibition of KIR channels and Na+-K+-ATPase alone [via barium chloride (BaCl2) and ouabain, respectively; trial 2(T2)]; and with additional combined nitric oxide synthase (NG-monomethyl-l-arginine) and cyclooxygenase inhibition [ketorolac; trial 3 (T3)]. In T2, the total hyperemic responses were attenuated ∼50% from control (P \u3c 0.05) at exercise onset, and there was minimal further effect in T3 (protocol 1; n= 11). In protocol 2 (n = 8), steady-state FBF was significantly reduced during T2 vs. T1 (133 ± 15 vs. 167 ± 17 ml/min; Δ from control: −20 ± 3%; P \u3c 0.05) and further reduced during T3 (120 ± 15 ml/min; −29 ± 3%; P \u3c 0.05 vs. T2). In protocol 3 (n = 8), BaCl2 alone reduced FBF during onset (∼50%) and steady-state exercise (∼30%) as observed in protocols 1 and 2, respectively, and addition of ouabain had no further impact. Our data implicate activation of KIR channels as a novel contributing pathway to exercise hyperemia in humans

    Reactive Hyperemia Occurs Via Activation of Inwardly Rectifying Potassium Channels and Na+/K+-ATPase in Humans

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    Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear. Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na+/K+-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans. Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 subjects and assessed RH in the following conditions. For group 1, we studied control (saline), KIR channel inhibition (BaCl2), combined inhibition of KIR channels and Na+/K+-ATPase (BaCl2 and ouabain, respectively), and combined inhibition of KIR channels, Na+/K+-ATPase, NO, and prostaglandins (BaCl2, ouabain, L-NMMA [NG-monomethyl-L-arginine] and ketorolac, respectively). Group 2 received ouabain rather than BaCl2 in the second trial. In protocol 2 (n=8), the following 3 RH trials were performed: control; L-NMMA plus ketorolac; and L-NMMA plus ketorolac plus BaCl2 plus ouabain. All infusions were intra-arterial (brachial). Compared with control, BaCl2 significantly reduced peak FBF (−50±6%; P2 (−61±3%) and ouabain (−44±12%) alone, and this effect was enhanced when combined (−87±4%), nearly abolishing RH. L-NMMA plus ketorolac did not impact total RH FBF before or after administration of BaCl2 plus ouabain. Conclusions: Activation of KIR channels is the primary determinant of peak RH, whereas activation of both KIR channels and Na+/K+-ATPase explains nearly all of the total (AUC) RH in humans

    Impaired Peripheral Vasodilation during Graded Systemic Hypoxia in Healthy Older Adults: Role of the Sympathoadrenal System

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    Systemic hypoxia is a physiological and pathophysiological stress that activates the sympathoadrenal system and, in young adults, leads to peripheral vasodilation. We tested the hypothesis that peripheral vasodilation to graded systemic hypoxia is impaired in older healthy adults and that this age-associated impairment is due to attenuated β-adrenergic mediated vasodilation and elevated α-adrenergic vasoconstriction. Forearm blood flow was measured (Doppler ultrasound) and vascular conductance (FVC) was calculated in 12 young (24±1 yrs) and 10 older (63±2 yrs) adults to determine the local dilatory responses to graded hypoxia (90, 85, and 80% O2 saturations) in control conditions, following local intra-arterial blockade of β-receptors (propranolol), and combined blockade of α+β receptors (phentolamine + propranolol). Under control conditions, older adults exhibited impaired vasodilation to hypoxia compared with young at all levels of hypoxia (peak ΔFVC at 80% SpO2 = 4±6 vs. 35±8%; P\u3c0.01). During β-blockade, older adults actively constricted at 85 and 80% SpO2 (peak ΔFVC at 80% SpO2= -13±6%; P\u3c0.05 vs. control) whereas the response in the young was not significantly impacted (peak ΔFVC = 28±8%). Combined α+β blockade increased the dilatory response to hypoxia in young adults, however older adults failed to significantly vasodilate (peak ΔFVC at 80% SpO2= 12±11% vs. 58±11%; P\u3c0.05). Our findings indicate that peripheral vasodilation to graded systemic hypoxia is significantly impaired in older adults which cannot be fully explained by altered sympathoadrenal control of vascular tone. Thus, the impairment in hypoxic vasodilation is likely due to attenuated local vasodilatory and/or augmented vasoconstrictor signaling with age

    Using a cognitive architecture to examine what develops

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    Different theories of development propose alternative mechanisms by which development occurs. Cognitive architectures can be used to examine the influence of each proposed mechanism of development while keeping all other mechanisms constant. An ACT-R computational model that matched adult behavior in solving a 21-block pyramid puzzle was created. The model was modified in three ways that corresponded to mechanisms of development proposed by developmental theories. The results showed that all the modifications (two of capacity and one of strategy choice) could approximate the behavior of 7-year-old children on the task. The strategy-choice modification provided the closest match on the two central measures of task behavior (time taken per layer, r = .99, and construction attempts per layer, r = .73). Modifying cognitive architectures is a fruitful way to compare and test potential developmental mechanisms, and can therefore help in specifying “what develops.

    The Gravity Field of Mercury After the Messenger Low-Altitude Campaign

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    The final year of the MESSENGER mission was designed to take advantage of the remaining propellant onboard to provide a series of lowaltitude observation campaigns and acquire novel scientific data about the innermost planet. The lower periapsis altitude greatly enhances the sensitivity to the short-wavelength gravity field, but only when the spacecraft is in view of Earth. After more than 3 years in orbit around Mercury, the MESSENGER spacecraft was tracked for the first time below 200-km altitude on 5 May 2014 by the NASA Deep Space Network (DSN). Between August and October, periapsis passages down to 25-km altitude were routinely tracked. These periods considerably improved the quality of the data coverage. Before the end of its mission, MESSENGER will fly at very low altitudes for extended periods of time. Given the orbital geometry, however the periapses will not be visible from Earth and so no new tracking data will be available for altitudes lower than ~75 km. Nevertheless, the continuous tracking of MESSENGER in the northern hemisphere will help improve the uniformity of the spatial coverage at altitudes lower than ~150 km, which will further improve the overall quality of the Mercury gravity field