Putative role of the NTS in alterations in neural control of the circulation following exercise training in rats

2006 ◽  
Vol 290 (2) ◽  
pp. R383-R392 ◽  
Author(s):  
Patrick J. Mueller ◽  
Eileen M. Hasser
Keyword(s):  
Exercise Training ◽  
Neural Control ◽  
Nucleus Tractus Solitarius ◽  
Arterial Baroreflex ◽  
Sprague Dawley ◽  
Glutamate Receptor Antagonist ◽  
Sprague Dawley Rats ◽  
Dose Dependent ◽  
Sedentary Conditions

Exercise training (ExTr) has been associated with alterations in neural control of the circulation, including effects on arterial baroreflex function. The nucleus tractus solitarius (NTS) is the primary termination site of cardiovascular afferents and critical in the regulation of baroreflex-mediated changes in heart rate (HR) and sympathetic nervous system outflow. The purpose of the present study was to determine whether ExTr is associated with alterations in neurotransmitter regulation of neurons involved in control of cardiovascular function at the level of the NTS. We hypothesized that ExTr would increase glutamatergic and reduce GABAergic transmission in the NTS and that, collectively, these changes would result in a greater overall sympathoinhibitory drive from the NTS in ExTr animals. To test these hypotheses, male Sprague-Dawley rats were treadmill trained or maintained under sedentary conditions for 8–10 wk. NTS microinjections were performed in Inactin-anesthetized animals instrumented to record mean arterial pressure (MAP), HR, and lumbar sympathetic nerve activity (LSNA). Generalized activation of the NTS with unilateral microinjections of glutamate (1–10 mM, 30 nl) produced dose-dependent decreases in MAP, HR, and LSNA that were unaffected by ExTr. Bilateral inhibition of NTS with the GABAA agonist muscimol (1 mM, 90 nl) produced increases in MAP and LSNA that were blunted by ExTr. In contrast, pressor and sympathoexcitatory responses to bilateral microinjections of the ionotropic glutamate receptor antagonist, kynurenate (40 mM, 90 nl), were similar between groups. Bradycardic responses to bilateral microinjections of the GABAA antagonist bicuculline (0.1 mM, 90 nl) were attenuated by ExTr. These data indicate that alterations in neurotransmission at the level of the NTS contribute importantly to regulation of HR and LSNA in ExTr animals. In addition to alterations at NTS, these experiments suggest indirectly that changes in other cardiovascular nuclei contribute to the observed alterations in neural control of the circulation following ExTr.

Dehydroepiandrosterone prevents dexamethasone-induced hypertension in rats

1992 ◽  
Vol 263 (2) ◽  
pp. E210-E213 ◽  
Author(s):  
Y. Shafagoj ◽  
J. Opoku ◽  
D. Qureshi ◽  
W. Regelson ◽  
M. Kalimi
Keyword(s):  
Weight Loss ◽  
Genetic Model ◽  
Experimental Hypertension ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Spontaneously Hypertensive ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Dose Dependent

Dehydroepiandrosterone (DHEA) is an endogenous steroid having a wide variety of biological and biochemical effects. In the present study, we have examined the role of DHEA on various rodent models of experimental hypertension. Sprague-Dawley rats were given subcutaneous injections of 1.5 mg dexamethasone every alternate day, resulting in an increase in systolic blood pressure within 1 wk. Interestingly, administration of a pharmacological dose of 1.5, 3, or 7.5 mg DHEA along with dexamethasone prevented dexamethasone-induced hypertension in a dose-dependent manner. DHEA had no effect on the hypertension induced by deoxycorticosterone acetate (DOCA)-salt administration using uninephrectomized rats or on the genetic model of spontaneously hypertensive rats. Dexamethasone administration resulted in a significant weight loss in rats, which was not prevented by simultaneous administration of DHEA. These results indicate that dexamethasone-mediated weight loss may involve mechanisms separate from its hypertensive action. Dexamethasone treatment resulted in a significant decrease in food consumption that was not reversed by DHEA. It is concluded that DHEA at doses above physiological levels when given subcutaneously has no effect on DOCA-salt or a genetic model of hypertension but has a beneficial effect on dexamethasone-induced hypertension.

Role of cytochrome P-450 in endogenous antipyresis

2000 ◽  
Vol 279 (2) ◽  
pp. R455-R460 ◽  
Author(s):  
Wieslaw Kozak ◽  
Matthew J. Kluger ◽  
Anna Kozak ◽  
Maciej Wachulec ◽  
Karol Dokladny
Keyword(s):  
Arachidonic Acid ◽  
Intraperitoneal Administration ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Rats And Mice ◽  
Dose Dependent ◽  
Cytochrome P 450

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 μg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 μg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.

Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic acids

2005 ◽  
Vol 289 (2) ◽  
pp. F386-F392 ◽  
Author(s):  
Elvira L. Liclican ◽  
John C. McGiff ◽  
Paulina L. Pedraza ◽  
Nicholas R. Ferreri ◽  
John R. Falck ◽  
...  
Keyword(s):  
High Salt ◽  
Gas Chromatography Mass Spectrometry ◽  
Epoxyeicosatrienoic Acids ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent ◽  
Cytochrome P 450 ◽  
Adenosine Analog ◽  
Krebs Buffer

Cytochrome P-450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) dilate rat preglomerular microvessels when adenosine2A receptors (A2AR) are stimulated. As high salt (HS) intake increases epoxygenase activity and adenosine levels, we hypothesized that renal adenosine responses would be greater in HS-fed rats. Male Sprague-Dawley rats were fed either HS (4.0% NaCl) or normal salt (NS; 0.4% NaCl) diet. On day 8, isolated kidneys were perfused with Krebs' buffer containing indomethacin (10 μM) and l-NAME (200 μM) and preconstricted to ∼150 mmHg with infusion of phenylephrine (10−7 M). Renal effluents were extracted for analysis of eicosanoids by gas chromatography-mass spectrometry. Bolus injections of the stable adenosine analog 2-chloroadenosine (2-CA; 0.1–10 μg) resulted in dose-dependent dilation; at 10 μg, perfusion pressure (PP) was lowered to a greater extent in the kidneys of HS rats compared with NS rats (−60 ± 4 vs. −31 ± 8 mmHg; P < 0.05) and the area of response was increased (27 ± 6 vs. 9 ± 4 mm2; P < 0.05), as was EET release (132 ± 23 vs. 38 ± 18 ng; P < 0.05). HS treatment increased A2AR and CYP2C23 protein expression. A selective epoxygenase inhibitor, MS-PPOH (12 μM), significantly reduced the response to 2-CA in HS rats; PP, area of response, and EET release decreased by 40, 70, and 81%, respectively, whereas lesser changes were evident in NS kidneys. Thus the greater vasodilator response to 2-CA seen in kidneys obtained from HS-fed rats was mediated by increased EET release. As EETs are renal vasodilator and natriuretic eicosanoids, interactions between adenosine and EETs may contribute to the adaptive response to HS intake.

scholarly journals Exercise training and muscle microvascular oxygenation: functional role of nitric oxide

2012 ◽  
Vol 113 (4) ◽  
pp. 557-565 ◽  
Author(s):  
Daniel M. Hirai ◽  
Steven W. Copp ◽  
Scott K. Ferguson ◽  
Clark T. Holdsworth ◽  
Danielle J. McCullough ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Exercise Training ◽  
Peak Oxygen Uptake ◽  
Sprague Dawley ◽  
No Donor ◽  
Phosphorescence Quenching ◽  
Metabolic Adaptations ◽  
Sprague Dawley Rats ◽  
Microvascular Oxygenation

Exercise training induces multiple adaptations within skeletal muscle that may improve local O2delivery-utilization matching (i.e., Po2mv). We tested the hypothesis that increased nitric oxide (NO) function is intrinsic to improved muscle Po2mv kinetics from rest to contractions after exercise training. Healthy young Sprague-Dawley rats were assigned to sedentary ( n = 18) or progressive treadmill exercise training ( n = 10; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min, −14% grade) groups. Po2mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP, NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (l-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained rats had greater peak oxygen uptake (V̇o2peak) than their sedentary counterparts (81 ± 1 vs. 72 ± 2 ml·kg−1·min−1, respectively; P < 0.05). Exercise-trained rats had significantly slower Po2mv fall throughout contractions (τ1; time constant for the first component) during control (sedentary: 8.1 ± 0.6; trained: 15.2 ± 2.8 s). Compared with control, SNP slowed τ1to a greater extent in sedentary rats (sedentary: 38.7 ± 5.6; trained: 26.8 ± 4.1 s; P > 0.05) whereas l-NAME abolished the differences in τ1between sedentary and trained rats (sedentary: 12.0 ± 1.7; trained: 11.2 ± 1.4 s; P < 0.05). Our results indicate that endurance exercise training leads to greater muscle microvascular oxygenation across the metabolic transient following the onset of contractions (i.e., slower Po2mv kinetics) partly via increased NO-mediated function, which likely constitutes an important mechanism for training-induced metabolic adaptations.

scholarly journals Large BP-dependent and -independent differences in susceptibility to nephropathy after nitric oxide inhibition in Sprague-Dawley rats from two major suppliers

2012 ◽  
Vol 302 (1) ◽  
pp. F173-F182 ◽  
Author(s):  
Karen Griffin ◽  
Aaron Polichnowski ◽  
Hector Licea-Vargas ◽  
Maria Picken ◽  
Jianrui Long ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Linear Regression Analysis ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Renal Vasoconstriction ◽  
Renal Autoregulation ◽  
Sprague Dawley Rats ◽  
The Relationship ◽  
Dose Dependent

The Nω-nitro-l-arginine methyl ester (l-NAME) model is widely employed to investigate the role of nitric oxide (NO) in renal injury. The present studies show that Sprague-Dawley rats from Harlan (H) and Charles River (CR) exhibit strikingly large differences in susceptibility to l-NAME nephropathy. After 4 wk of l-NAME (∼50 mg·kg−1·day−1 in drinking water), H rats ( n = 13) exhibited the expected hypertension [average radiotelemetric systolic blood pressure (BP), 180 ± 3 mmHg], proteinuria (136 ± 17 mg/24 h), and glomerular injury (GI) (12 ± 2%). By contrast, CR rats developed less hypertension (142 ± 4), but surprisingly no proteinuria or GI, indicating a lack of glomerular hypertension. Additional studies showed that conscious H, but not CR, rats exhibit dose-dependent renal vasoconstriction after l-NAME. To further investigate these susceptibility differences, l-NAME was given 2 wk after 3/4 normotensive nephrectomy (NX) and comparably impaired renal autoregulation in CR-NX and H-NX rats. CR-NX rats, nevertheless, still failed to develop proteinuria and GI despite moderate hypertension (144 ± 2 mmHg, n = 29). By contrast, despite an 80–90% l-NAME dose reduction and lesser BP increases (169 ± 4 mmHg), H-NX rats ( n = 20) developed greater GI (26 ± 3%) compared with intact H rats. Linear regression analysis showed significant ( P < 0.01) differences in the slope of the relationship between BP and GI between H-NX (slope 0.56 ± 0.14; r = 0.69; P < 0.008) and CR-NX (slope 0.09 ± 0.06; r = 0.29; P = 0.12) rats. These data indicate that blunted BP responses to l-NAME in the CR rats are associated with BP-independent resistance to nephropathy, possibly mediated by a resistance to the renal (efferent arteriolar) vasoconstrictive effects of NO inhibition.

Abstract 293: Brain Gai2 Proteins Mediate Acute Neural Blood Pressure Responses to Centrally and Peripherally Administered NaCl

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Casey Y Carmichael ◽  
Sarah Mahne ◽  
Richard D Wainford
Keyword(s):  
Blood Pressure ◽  
Neural Control ◽  
Sprague Dawley ◽  
Baroreflex Control ◽  
High Salt Diet ◽  
Pharmacological Challenge ◽  
Sprague Dawley Rats ◽  
Blood Pressures ◽  
Blood Pressure Responses

Aim: We have demonstrated hypertension mediated by failure to upregulate PVN Gαi 2 proteins in rats fed a chronic high salt diet, but the role of this mechanism is unknown in acute settings. We examined the effect of central Gαi 2 proteins in the neural control of blood pressure in response to an acute physiological (IV and ICV) and pharmacological challenge. Methods: Twenty-four hour (24-h) ICV Gαi 2 or SCR oligodeoxynucleotide (ODN; 25μg/5μl)-pretreated conscious Sprague-Dawley rats were continuously monitored for changes in HR and MAP in response to peripherally-administered NaCl (3M IV bolus; 0.14 ml/100g) or centrally-administered NaCl (1M ICV; 5μL)(N=4/gp). To determine the cardiac baroreflex MAP was slowly raised to ~175 mmHg using phenylephrine and lowered to ~50 mmHg using sodium nitroprusside in separate group of pre-treated rats (N=8/gp). Results: In response to IV sodium, peak changes in HR were significantly greater in SCR vs. Gαi 2 treated rats (IV 3M NaCl ΔHR [bpm]; SCR -79±15 vs . Gαi 2 -59±12, P<0.05), but no difference was observed in peak changes in MAP (IV 3M NaCl ΔMAP [mmHg] SCR 147±4 mmHg vs . Gαi 2 149±3). In SCR rats, MAP returned to baseline by 100 min whereas Gαi 2 rats remained significantly elevated for 120 min (P<0.05). In response to ICV sodium, we observed no difference between groups in peak HR changes (ICV 1M NaCl ΔHR [bpm] -23±8 bpm vs . Gαi 2 -22±8) or peak MAP changes (ICV 1M NaCl ΔMAP [mmHg] 16±3 mmHg vs . Gαi 2 9±3). In SCR rats, MAP returned to baseline by 50 min whereas Gαi 2 rats remained elevated for 90 min. The 24h Gαi 2 ODN pretreatment significantly altered the high-, but not low-pressure gain of the baroreflex in response to pharmacological challenge (MAP=180 mmHg, SCR HR=270 bpm, Gαi 2 HR=307 bpm, P<0.05). Conclusion: Downregulation of Gαi 2 proteins resulted in altered cardiac baroreflex function by impairing reflex decreases in HR and mediating significantly prolonged elevated MAP in response to peripherally administered sodium. This highlights a previously undiscovered role of brain Gαi 2 proteins in the baroreflex control of HR at elevated blood pressures—a factor that may contribute to elevated MAP in neurogenic models of hypertension.

Mechanisms mediating regional sympathoactivatory responses to stimulation of NTS A1 adenosine receptors

2002 ◽  
Vol 283 (4) ◽  
pp. H1588-H1599 ◽  
Author(s):  
Tadeusz J. Scislo ◽  
Donal S. O'Leary
Keyword(s):  
Sympathetic Nerve Activity ◽  
Nucleus Tractus Solitarius ◽  
Glutamatergic Transmission ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sprague Dawley Rats ◽  
Afferent Inputs ◽  
A1 Adenosine Receptors ◽  
Dose Dependent ◽  
Stimulation Of

Selective activation of adenosine A1 and A2a receptors in the subpostremal nucleus tractus solitarius (NTS) increases and decreases mean arterial pressure (MAP), respectively, and decreases heart rate (HR). We have previously shown that the decreases in MAP evoked by NTS A2a receptor stimulation were accompanied with differential sympathetic responses in renal (RSNA), lumbar (LSNA), and preganglionic adrenal sympathetic nerve activity (pre-ASNA). Therefore, now we investigated whether stimulation of NTS A1 receptors via unilateral microinjection of N 6-cyclopentyladenosine (CPA) elicits differential activation of the same sympathetic outputs in α-chloralose-urethane-anesthetized male Sprague-Dawley rats. CPA (0.33–330.0 pmol in 50 nl) evoked dose-dependent increases in MAP, variable decreases in HR, and differential increases in all recorded sympathetic outputs: ↑pre-ASNA ≫↑RSNA ≥ ↑LSNA. Sinoaortic denervation + vagotomy abolished the MAP and LSNA responses, reversed the normal increases in RSNA into decreases, and significantly attenuated increases in pre-ASNA. NTS ionotropic glutamatergic receptor blockade with kynurenate sodium (4.4 nmol/100 nl) reversed the responses in MAP, LSNA, and RSNA and attenuated the responses in pre-ASNA. We conclude that afferent inputs and intact glutamatergic transmission in the NTS are necessary to mediate the pressor and differential sympathoactivatory responses to stimulation of NTS A1 receptors.

Participation of galanin in baroreflex inhibition of heart rate by hypothalamic PVN in rat

1996 ◽  
Vol 271 (5) ◽  
pp. H1823-H1828 ◽  
Author(s):  
Y. L. Chen ◽  
S. H. Chan ◽  
J. Y. Chan
Keyword(s):  
Heart Rate ◽  
Nucleus Tractus Solitarius ◽  
Chemical Activation ◽  
Cardiovascular Regulation ◽  
Baroreceptor Reflex ◽  
Local Administration ◽  
Sprague Dawley ◽  
Pentobarbital Sodium ◽  
Sprague Dawley Rats

We investigated the role of galanin (Gal) in the suppression of baroreceptor reflex (BRR) response by the paraventricular nucleus of the hypothalamus (PVN) in adult male Sprague-Dawley rats that were anesthetized with pentobarbital sodium. Electrical stimulation (10-s train of 1-ms rectangular pulses at 20-40 microA and 10-20 Hz) of, and microinjection of L-glutamate (1 nmol) into, the PVN significantly inhibited BRR response to transient hypertension induced by phenylephrine (5 micrograms/kg iv). Such a PVN-induced BRR suppression was appreciably antagonized by local administration of Gal antiserum (1:20), but not heat-inactivated Gal antiserum (1:20), to the nucleus tractus solitarius (NTS) bilaterally. Microinjection of Gal (100 pmol) into the NTS bilaterally also resulted in a Gal antiserum-reversible inhibition of the BRR response. Immunohistochemical results demonstrated that the distribution of Gal-containing neurons in the parvocellular subnucleus of the PVN overlapped substantially with the hypothalamic loci on which electrical or chemical activation elicited suppression of the BRR response that was significantly blunted by microinjection of Gal antiserum into the NTS. These results suggest that the PVN may participate in central cardiovascular regulation by suppressing the BRR response via galaninergic neurotransmission at the NTS.

scholarly journals Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

2011 ◽  
Vol 300 (5) ◽  
pp. H1781-H1787 ◽  
Author(s):  
Sachin S. Kandlikar ◽  
Gregory D. Fink
Keyword(s):  
Control Period ◽  
Whole Body ◽  
Renal Nerves ◽  
Experimental Hypertension ◽  
Sympathetic Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salt Hypertension ◽  
Hypertension Development

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration ( day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Chronic intravenous administration of V1 arginine vasopressin agonist results in sustained hypertension

1994 ◽  
Vol 267 (2) ◽  
pp. H751-H756 ◽  
Author(s):  
A. W. Cowley ◽  
E. Szczepanska-Sadowska ◽  
K. Stepniakowski ◽  
D. Mattson
Keyword(s):  
Body Weight ◽  
Arginine Vasopressin ◽  
Plasma Catecholamines ◽  
Plasma Osmolality ◽  
Sprague Dawley ◽  
Prolonged Administration ◽  
Chronic Stimulation ◽  
Sustained Hypertension ◽  
Sprague Dawley Rats

Despite the well-recognized vasoconstrictor and fluid-retaining actions of vasopressin, prolonged administration of arginine vasopressin (AVP) to normal animals or humans fails to produce sustained hypertension. The present study was performed to elucidate the role of the V1 receptor in determining the ability of AVP to produce sustained hypertension. Conscious Sprague-Dawley rats with implanted catheters were infused with the selective V1 agonist, [Phe2,Ile3,Orn8]vasopressin (2 ng.kg-1.min-1), for 14 days in amounts that were acutely nonpressor. Blood pressure (MAP), heart rate (HR), body weight, and water intake (WI) were determined daily. Plasma AVP, plasma catecholamines norepinephrine and epinephrine, plasma osmolality, and electrolyte concentration were determined before and on days 1 and 7 of infusion. MAP increased significantly by 10.4 +/- 4.5 mmHg on day 1 and rose to 22 +/- 5 mmHg above control by day 14 (transient decrease on days 6-9) and then fell to control levels after the infusion was stopped. HR did not change significantly. Plasma AVP immunoreactivity increased from 2.5 +/- 0.3 to 10.9 +/- 2.1 pg/ml, whereas norepinephrine tended to fall only on day 1, with epinephrine only slightly elevated on day 7. No evidence of fluid retention was found, and rats lost sodium only on the first day of V1 agonist infusion. Body weight increased throughout the study but was unrelated to the changes of MAP. We conclude that chronic stimulation of V1 receptors results in sustained hypertension in rats.

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