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Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites.
Harris RC, Munger KA, Badr KF, Takahashi K
(1990) FASEB J 4: 1654-60
MeSH Terms: 5,8,11,14-Eicosatetraynoic Acid, Animals, Arachidonic Acid, Arachidonic Acids, Blood Pressure, Bridged Bicyclo Compounds, Heterocyclic, Dinoprost, Epidermal Growth Factor, Fatty Acids, Unsaturated, Glomerular Filtration Rate, Hydrazines, Ibuprofen, Ketoconazole, Kidney, Rats, Receptors, Prostaglandin, Receptors, Thromboxane, Regional Blood Flow
Show Abstract · Added August 19, 2013
In the rat, intrarenal infusion of epidermal growth factor decreases renal blood flow and glomerular filtration rate, and epidermal growth factor (EGF) induces contraction of cultured rat mesangial cells. The present studies examined the role of arachidonic acid metabolites in this response. Intrarenal EGF infusion increased urinary iPGF2 alpha by 300%, and in isolated glomeruli EGF stimulated iPGF2 alpha by 38%, but did not affect thromboxane B2 production. Furthermore, the thromboxane A2 receptor antagonist, SQ29548, did not block EGF's vasoconstrictive effects. After selective cyclooxygenase inhibition with ibuprofen, intrarenal EGF infusion no longer produced local vasoconstriction but instead led to systemic vasodilation (SBP: 117 +/- 10 vs. 98 +/- 7; n = 5; P less than 0.05) that was accompanied by significant increases in RPF (3.8 +/- 0.4 vs. 5.6 +/- 0.2; P less than 0.01) and glomerular filtration rate (0.9 +/- 0.1 vs. 1.1 +/- 0.1; P less than 0.05). When total arachidonate metabolism was inhibited by the additional administration of 5,8,11,14-eicosatetraynoic acid, the EGF-induced vasodilation observed during cyclooxygenase inhibition alone was abolished, and vasoconstrictor responses to EGF were again noted. Similar effects were noted with concomitant administration of the c-P450 inhibitor ketoconazole. EGF's vasoconstrictive effects were unaltered by the simultaneous administration of the angiotensin II antagonist saralasin. Thus, the renal hemodynamic responses to EGF are mediated in part by arachidonic acid metabolites. Cyclooxygenase inhibition unmasks a potent renal and systemic vasodilator action of EGF owing to its stimulation of systemic release of noncyclooxygenase arachidonate metabolites.
1 Communities
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18 MeSH Terms
Intraportal glucose delivery alters the relationship between net hepatic glucose uptake and the insulin concentration.
Myers SR, McGuinness OP, Neal DW, Cherrington AD
(1991) J Clin Invest 87: 930-9
MeSH Terms: Animals, Biological Transport, Blood Glucose, Dogs, Female, Glucagon, Glucose, Hepatic Artery, Insulin, Lactates, Liver, Male, Portal Vein, Regional Blood Flow
Show Abstract · Added December 10, 2013
To examine the relationship between net hepatic glucose uptake (NHGU) and the insulin level and to determine the effects of portal glucose delivery on that relationship, NHGU was evaluated at three different insulin levels in seven 42-h-fasted, conscious dogs during peripheral glucose delivery and during a combination of peripheral and portal glucose delivery. During peripheral glucose delivery, at arterial blood glucose levels of approximately 175 mg/dl and insulin levels reaching the liver of 51 +/- 2, 92 +/- 6, and 191 +/- 6 microU/ml, respectively, NHGUs were 0.55 +/- 0.30, 1.52 +/- 0.44, and 3.04 +/- 0.79 mg/kg per min, respectively. At hepatic glucose loads comparable to those achieved during peripheral glucose delivery and inflowing insulin levels of 50 +/- 4, 96 +/- 5, and 170 +/- 8 microU per ml, respectively, NHGUs were 1.96 +/- 0.48, 3.67 +/- 0.68, and 5.52 +/- 0.92 mg/kg per min when a portion of the glucose load was delivered directly into the portal vein. The results of these studies thus indicate that net hepatic glucose uptake is dependent on both the plasma insulin level and the route of glucose delivery and that under physiological conditions the "portal" signal is at least as important as insulin in the determination of net hepatic glucose uptake.
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14 MeSH Terms
Interaction of gut and liver in nitrogen metabolism during exercise.
Wasserman DH, Geer RJ, Williams PE, Becker T, Lacy DB, Abumrad NN
(1991) Metabolism 40: 307-14
MeSH Terms: Alanine, Ammonia, Animals, Dogs, Glutamates, Glutamic Acid, Glutamine, Hepatic Artery, Intestinal Mucosa, Liver, Nitrogen, Physical Exertion, Portal Vein, Regional Blood Flow, Splanchnic Circulation, Urea
Show Abstract · Added December 10, 2013
The role of the gut and liver in nitrogen metabolism was studied during rest, 150 minutes of moderate-intensity treadmill exercise, and 90 minutes of recovery in 18 hour-fasted dogs (n = 6). Dogs underwent surgery 16 days before an experiment for implantation of catheters in a carotid artery and in the portal and hepatic veins, and Doppler flow cuffs on the hepatic artery and portal vein. Arterial glutamine, alanine, and alpha-amino nitrogen (AAN) levels decreased gradually with exercise (P less than .05), while arterial glutamate, NH3, and urea were unchanged. Net gut glutamine uptake was 1.3 +/- 0.5 mumol/kg.min at rest, and increased transiently to 2.5 +/- 0.3 mumol/kg.min at 60 minutes of exercise (P less than .05) as gut extraction increased. Net hepatic glutamine uptake was 0.6 +/- 0.4 mumol/kg.min at rest, and increased to 3.4 +/- 0.6 and 2.6 +/- 0.5 mumol/kg.min after 60 and 150 minutes of exercise (P less than .05) as hepatic extraction increased. Net gut glutamate and NH3 output both increased transiently with exercise (P less than .05). These increases were matched by parallel increments in the net hepatic uptakes of these compounds. Alanine output by the gut and uptake by the liver were unchanged with exercise. Net gut AAN output was -2.1 +/- 1.8 mumol/kg.min at rest (uptake occurred), and increased transiently to 11.2 +/- 3.5 mumol/kg.min after 30 minutes of exercise (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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16 MeSH Terms
Effects of head-down tilt for 10 days on the compliance of the leg.
Buckey JC, Lane LD, Plath G, Gaffney FA, Baisch F, Blomqvist CG
(1992) Acta Physiol Scand Suppl 604: 53-9
MeSH Terms: Adaptation, Physiological, Adult, Analysis of Variance, Blood Pressure, Humans, Hypotension, Orthostatic, Leg, Male, Plasma Volume, Regional Blood Flow, Space Flight, Supine Position, Vascular Resistance, Weightlessness
Show Abstract · Added May 20, 2014
The purpose of this investigation was to measure lower leg compliance before, during and after a 10-day period of bedrest at head-down tilt to test the hypothesis that leg compliance and the capacity for venous pooling is increased by the adaptation to stimulated microgravity. Venous occlusion plethysmography with multiple proximal occlusion pressures was used to obtain compliance measurements in six male subjects. Calf circumference decreased significantly during the tilt (corresponding to a decrease in cross sectional area of 7%) and had not returned to baseline seven days after the end of tilt. Compliance post-tilt was significantly greater than pre-tilt, probably mainly due to a reduction in muscle mass. This study supports the need for investigations to define: (a) the degree of protection against orthostatic hypotension that can be achieved by maintaining leg muscle mass and tone, and (b) efficient and specific exercise programs to prevent loss of muscle mass and function-particularly during spaceflight.
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14 MeSH Terms
Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.
Watenpaugh DE, Yancy CW, Buckey JC, Lane LD, Hargens AR, Blomqvist CG
(1992) J Appl Physiol (1985) 73: 1218-26
MeSH Terms: Adult, Atrial Natriuretic Factor, Blood Pressure, Blood Volume, Cardiac Catheterization, Cardiac Output, Echocardiography, Heart Rate, Hematocrit, Hemodilution, Humans, Isotonic Solutions, Leg, Male, Pressoreceptors, Regional Blood Flow, Urodynamics
Show Abstract · Added May 20, 2014
Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)
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17 MeSH Terms
Impact of insulin deficiency on glucose fluxes and muscle glucose metabolism during exercise.
Wasserman DH, Mohr T, Kelly P, Lacy DB, Bracy D
(1992) Diabetes 41: 1229-38
MeSH Terms: Analysis of Variance, Animals, Blood Glucose, Blood Pressure, Dogs, Epinephrine, Fatty Acids, Nonesterified, Female, Glucagon, Glucose, Heart Rate, Homeostasis, Hydrocortisone, Insulin, Male, Muscles, Norepinephrine, Physical Conditioning, Animal, Reference Values, Regional Blood Flow, Somatostatin
Show Abstract · Added August 19, 2014
Exercise in the insulin-deficient diabetic state is characterized by a further increase in elevated circulating glucose and NEFA levels and by excessive counterregulatory hormone levels. The aim of this study was to distinguish the direct glucoregulatory effects of insulinopenia during exercise from the indirect effects that result from the metabolic and hormonal environment that accompanies insulin deficiency. For this purpose, dogs underwent 90 min of treadmill exercise during SRIF infusion with (SRIF + INS, n = 8) or without (SRIF - INS, n = 6) intraportal insulin replacement. Glucagon was not replaced, thus allowing assessment of the direct effect of insulinopenia at the liver independent of the potentiation of glucagon action. Glucose was infused to maintain euglycemia. Hepatic glucose production (Ra); glucose utilization (Rd); and LGlcU, LGlcE, and LGlcO were assessed with tracers ([3H]glucose, [14C]glucose) and arteriovenous differences. With exercise, insulin fell from 66 +/- 6 to 42 +/- 6 pM in the SRIF + INS group, and was undetectable in the SRIF - INS group. Plasma glucose was 6.33 +/- 0.38 and 6.26 +/- 0.30 mM at rest in the SRIF + INS and SRIF - INS groups, respectively, and was unchanged with exercise. Ra rose from 7.5 +/- 2.3 to 16.5 +/- 2.2 mumol.kg-1.min-1 and 9.1 +/- 2.0 to 31.4 +/- 3.9 mumol.kg-1.min-1 with exercise in the SRIF + INS and SRIF - INS groups, whereas Rd rose from 19.5 +/- 2.0 to 46.8 +/- 3.9 mumol.kg-1.min-1 and 15.1 +/- 1.8 to 29.9 +/- 3.3 mumol.kg-1.min-1. LGlcU rose from 36 +/- 9 to 112 +/- 25 mumol/min and 15 +/- 4 to 59 +/- 13 mumol/min and LGlcO rose from 5 +/- 2 to 61 +/- 12 mumol/min and 5 +/- 3 to 32 +/- 9 mumol/min with exercise in the SRIF+INS and SRIF-INS groups, respectively. Arterial levels and limb balances of NEFAs and glycerol were similar in the two groups. In summary, during exercise: 1) marked insulinopenia attenuates the increases in muscle glucose uptake and oxidation by approximately 50%, independent of changes in circulating metabolic substrate levels; 2) substantial increases in muscle glucose uptake and oxidation are, however, still present even in the absence of detectable insulin levels; and 3) insulinopenia facilitates the increase in Ra, independent of the potentiation of basal glucagon action. In conclusion, marked insulinopenia contributes directly to the exacerbation of glucoregulation during exercise in the diabetic state by limiting the rises in glucose uptake and metabolism and by enhancing hepatic glucose production.
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21 MeSH Terms
Ketone body turnover and net hepatic ketone production in fasted and diabetic dogs.
Keller U, Cherrington AD, Liljenquist JE
(1978) Am J Physiol 235: E238-47
MeSH Terms: Acetoacetates, Alloxan, Animals, Blood Glucose, Diabetes Mellitus, Experimental, Dogs, Fasting, Fatty Acids, Nonesterified, Female, Glucagon, Hydroxybutyrates, Ketone Bodies, Liver, Male, Regional Blood Flow
Added December 10, 2013
0 Communities
1 Members
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15 MeSH Terms
Skeletal muscle bloodflow, bloodgas and electrolyte changes after 1-3 hours of arterial occlusion in man.
Larsson J, Lewis DH, Liljedahl SO, Löfström JB
(1977) Bibl Anat : 559-62
MeSH Terms: Carbon Dioxide, Humans, Hydrogen-Ion Concentration, Ischemia, Leg, Muscles, Oxygen, Potassium, Regional Blood Flow, Sodium
Added February 9, 2015
1 Communities
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10 MeSH Terms