Splanchnic and renal contribution to disposal of infused epinephrine in humans

1986 ◽  
Vol 251 (3) ◽  
pp. E285-E289
Author(s):  
L. Sacca ◽  
R. Hendler ◽  
A. Picardi ◽  
R. S. Sherwin
Keyword(s):  
Plasma Flow ◽  
Renal Vein ◽  
Renal Plasma Flow ◽  
Plasma Epinephrine ◽  
Great Efficiency ◽  
Hemodynamic Changes ◽  
Epinephrine Infusion ◽  
Human Volunteers ◽  
Vein Catheterization

To evaluate the role of splanchnic and renal tissues in epinephrine disposal, we infused epinephrine (60 ng X kg-1 X min-1) into nine human volunteers during hepatic (n = 6) and/or renal (n = 4) vein catheterization. During the infusion plasma epinephrine rose higher in the artery (1,345 +/- 126 pg/ml) than in the hepatic (218 +/- 42 pg/ml) or renal vein (528 +/- 95 pg/ml). Splanchnic plasma flow increased by 43% (P less than 0.001), whereas renal plasma flow was unchanged. Net epinephrine uptake increased to a greater extent (3-fold) in the splanchnic area as compared with the kidney, amounting to 32 +/- 3% and 10 +/- 2% of the infused epinephrine load, respectively. The splanchnic epinephrine clearance also increased by 50-60%, while fractional extraction remained stable at 80-85%. Renal epinephrine clearance and extraction was not significantly altered, however. Epinephrine infusion caused splanchnic norepinephrine uptake to increase as well, partially because of the increased plasma flow. In contrast, the kidney showed net norepinephrine production throughout. We conclude that the splanchnic area plays a much more important role than the kidney in the disposal of circulating epinephrine. The great efficiency of splanchnic epinephrine removal is further enhanced by epinephrine-induced hemodynamic changes that also promote the splanchnic uptake of norepinephrine.

scholarly journals Plasma Epinephrine Contributes to the Development of Experimental Hypoglycemia-Associated Autonomic Failure

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Eric Lontchi-Yimagou ◽  
Sandra Aleksic ◽  
Raphael Hulkower ◽  
Rebekah Gospin ◽  
Akankasha Goyal ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Interindividual Variability ◽  
Autonomic Failure ◽  
Plasma Epinephrine ◽  
Epinephrine Infusion ◽  
Hypoglycemic Episode ◽  
The Third ◽  
Key Features ◽  
Recurrent Hypoglycemia

Abstract Background Recurrent hypoglycemia blunts counter-regulatory responses to subsequent hypoglycemic episodes, a syndrome known as hypoglycemia-associated autonomic failure (HAAF). Since adrenergic receptor blockade has been reported to prevent HAAF, we investigated whether the hypoglycemia-associated rise in plasma epinephrine contributes to pathophysiology and reported interindividual differences in susceptibility to HAAF. Methods To assess the role of hypoglycemia-associated epinephrine responses in the susceptibility to HAAF, 24 adult nondiabetic subjects underwent two 2-hour hyperinsulinemic hypoglycemic clamp studies (nadir 54 mg/dL; 0-2 hours and 4-6 hours) on Day 1, followed by a third identical clamp on Day 2. We challenged an additional 7 subjects with two 2-hour infusions of epinephrine (0.03 μg/kg/min; 0-2 hours and 4-6 hours) vs saline on Day 1 followed by a 200-minute stepped hypoglycemic clamp (90, 80, 70, and 60 mg/dL) on Day 2. Results Thirteen out of 24 subjects developed HAAF, defined by ≥20% reduction in average epinephrine levels during the final 30 minutes of the third compared with the first hypoglycemic episode (P < 0.001). Average epinephrine levels during the final 30 minutes of the first hypoglycemic episode were 2.3 times higher in subjects who developed HAAF compared with those who did not (P = 0.006). Compared to saline, epinephrine infusion on Day 1 reduced the epinephrine responses by 27% at the 70 and 60 mg/dL glucose steps combined (P = 0.04), with a parallel reduction in hypoglycemic symptoms (P = 0.03) on Day 2. Conclusions Increases in plasma epinephrine reproduce key features of HAAF in nondiabetic subjects. Marked interindividual variability in epinephrine responses to hypoglycemia may explain an individual’s susceptibility to developing HAAF.

scholarly journals Nitric oxide: a potential mediator of amino acid-induced renal hyperemia and hyperfiltration.

1991 ◽  
Vol 1 (12) ◽  
pp. 1271-1277
Author(s):  
A J King ◽  
J L Troy ◽  
S Anderson ◽  
J R Neuringer ◽  
M Gunning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glomerular Filtration Rate ◽  
Amino Acid ◽  
Glomerular Filtration ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Competitive Inhibitor ◽  
Arterial Blood

The role of nitric oxide in the modulation of systemic and renal hemodynamics was examined by using N omega-monomethyl-L-arginine (L-NMMA, 110 micrograms/kg/min), a competitive inhibitor of the conversion of L-arginine to nitric oxide. L-NMMA or saline vehicle (9.6 microL/min) was infused intravenously into anesthetized euvolemic Munich-Wistar rats. After 30 min, L-NMMA resulted in a uniform increase in mean arterial blood pressure (111 +/- 1 to 128 +/- 2 mmHg; P less than 0.05) and a modest reduction in renal plasma flow rate (4.4 +/- 0.2 to 4.2 +/- 0.1 mL/min; P less than 0.05), without change in glomerular filtration rate (1.16 +/- 0.03 to 1.15 +/- 0.03 mL/min); vehicle had no effect on these renal parameters. These rats were then subdivided to receive an intravenous infusion (37 microL/min) of either 10% glycine, 11.4% mixed amino acids, or equiosmolar dextrose. L-NMMA pretreatment markedly attenuated glycine-induced hyperfiltration (10 +/- 6 versus 33 +/- 5%, L-NMMA versus vehicle; P less than 0.05) and obliterated the renal hyperemic response (-7 +/- 6 versus 16 +/- 4%, L-NMMA versus vehicle; P less than 0.05). L-NMMA also caused modest blunting of the mixed amino acid-induced hyperfiltration (18 +/- 4 versus 30 +/- 4%, L-NMMA versus vehicle; P = 0.056) but failed to curtail the renal hyperemia (16 +/- 6 versus 20 +/- 4%). Dextrose had no effect on glomerular filtration rate or renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of deep nephrons and the terminal collecting duct in a mannitol-induced diuresis

1981 ◽  
Vol 240 (5) ◽  
pp. F411-F422 ◽  
Author(s):  
J. Buerkert ◽  
D. Martin ◽  
J. Prasad ◽  
D. Trigg
Keyword(s):  
Plasma Flow ◽  
Collecting Duct ◽  
Renal Plasma Flow ◽  
Distal Tubule ◽  
Sodium Reabsorption ◽  
Water Reabsorption ◽  
Single Nephron ◽  
Papillary Collecting Duct ◽  
Reduced Water

Recollection micropuncture in Munich-Wistar rats was used to study the effects of intravenous hypertonic mannitol infusions on fluid reabsorption by surface nephrons, prior to the bend of Henle's loop of deep nephrons, and along the papillary collecting duct. During mannitol diuresis, single nephron glomerular filtration rate rose significantly in surface nephrons but fell in deep nephrons. Although mannitol increased the delivery of sodium and water to the end of the proximal tubule and to the first portion of the distal tubule of surface nephrons, water and sodium were reabsorbed between these two sites. In deep nephrons, water reabsorption prior to the bend of the loop of Henle was significantly decreased. Absolute sodium delivery to this site was reduced despite a marked decrease in fractional sodium reabsorption prior to the bend. Papillary osmolality was decreased. Renal plasma flow and inner medullary plasma flow (IMPF) increased proportionally. The reduced water extraction prior to the bend of deep nephrons and the decrease in papillary osmolality could have been partly due to a concomitant increase in IMPF and a decrease in sodium delivery to the medulla. The reabsorption of delivered sodium and water by the papillary collecting duct was reduced to a greater extent than could be expected from the increase in sodium delivery.

Role of neuronal nitric oxide synthase in mediating renal hemodynamic changes during pregnancy

2001 ◽  
Vol 281 (5) ◽  
pp. R1390-R1393 ◽  
Author(s):  
S. R. Abram ◽  
B. T. Alexander ◽  
W. A. Bennett ◽  
J. P. Granger
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Renal Plasma Flow ◽  
Neuronal Nitric Oxide Synthase ◽  
Hemodynamic Changes ◽  
Pregnant Rats ◽  
Renal Hemodynamic ◽  
Oxide Synthase ◽  
Nnos Inhibition

Renal plasma flow (RPF) and glomerular filtration rate (GFR) are markedly increased during pregnancy. We recently reported that the renal hemodynamic changes observed during pregnancy in rats are associated with enhanced renal protein expression of neuronal nitric oxide synthase (nNOS). The purpose of this study was to determine the role of nNOS in mediating renal hemodynamic changes observed during pregnancy. To achieve this goal, we examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) on kidney function in normal conscious, chronically instrumented virgin ( n = 6) and pregnant rats ( n = 9) at day 16 of gestation. Infusion of 7-NI had no effect on RPF (4.7 ± 0.7 vs. 4.8 ± 0.9 ml/min), GFR (2.2 ± 0.2 vs. 2.5 ± 0.4 ml/min), or mean arterial pressure (MAP; 127 ± 7 vs. 129 ± 10 mmHg) in virgin rats. In contrast, 7-NI infused into pregnant rats decreased RPF (8.9 ± 1.6 vs. 6.5 ± 1.4 ml/min) and GFR (4.4 ± 0.7 vs. 3.3 ± 0.7 ml/min) while having no effect on MAP (123 ± 4 vs. 123 ± 3 mmHg). In summary, inhibition of nNOS in pregnant rats at midgestation results in significant decreases in RPF and GFR. nNOS inhibition in virgin rats had no effect on renal hemodynamics. These data suggest that nNOS may play a role in mediating the renal hemodynamic changes that occur during pregnancy.

Role of neuronal nitric oxide synthase (NOS1) in the pathogenesis of renal hemodynamic changes in diabetes

2000 ◽  
Vol 279 (3) ◽  
pp. F573-F583 ◽  
Author(s):  
Radko Komers ◽  
Jessie N. Lindsley ◽  
Terry T. Oyama ◽  
Kristen M. Allison ◽  
Sharon Anderson
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Renal Plasma Flow ◽  
Diabetic Rats ◽  
Hemodynamic Changes ◽  
Renal Hemodynamic ◽  
Streptozotocin Diabetic Rats ◽  
Oxide Synthase ◽  
Nos Isoforms

Nitric oxide (NO) has been implicated in the pathogenesis of renal hemodynamic changes in diabetes mellitus. However, the contribution of nitric oxide synthase (NOS) isoforms to intrarenal production of NO in diabetes remains unknown. To explore the role of NOS1 in the control of renal hemodynamics in diabetes, we assessed renal responses to inhibition of NOS1 with S-methyl-l-thiocitrulline (SMTC; administered into the abdominal aorta) in moderately hyperglycemic streptozotocin-diabetic rats (D) and their nondiabetic (C) and normoglycemic diabetic counterparts. The contribution of other NOS isoforms was also evaluated by assessing the responses to nonspecific NOS inhibition [ N G-nitro-l-arginine methyl ester (l-NAME)] in SMTC-treated diabetic rats. The number of NOS1-positive cells in macula densa of D and C kidneys was also evaluated by immunohistochemistry. D rats demonstrated elevated glomerular filtration rate (GFR) compared with C. SMTC (0.05 mg/kg) normalized GFR in D but had no effect in C. SMTC-induced reduction of renal plasma flow (RPF) was similar in C and D. Normoglycemic diabetic rats demonstrated blunted renal hemodynamic responses to NOS1 inhibition compared with hyperglycemic animals. Mean arterial pressure was stable in all groups. l-NAME induced a further decrease in RPF, but not in GFR, in D rats treated with SMTC. Immunohistochemistry revealed increased numbers of NOS1-positive cells in D. These observations suggest that NOS1-derived NO plays a major role in the pathogenesis of renal hemodynamic changes early in the course of diabetes. NOS1 appears to be the most important isoform in the generation of hemodynamically active NO in this condition.

Effect of epinephrine on glucose disposal during exercise in humans: role of muscle glycogen

2002 ◽  
Vol 283 (3) ◽  
pp. E578-E583 ◽  
Author(s):  
Matthew J. Watt ◽  
Mark Hargreaves
Keyword(s):  
Muscle Glycogen ◽  
Glucose Disposal ◽  
Plasma Epinephrine ◽  
Epinephrine Infusion ◽  
Low Carbohydrate Diet ◽  
Low Carbohydrate ◽  
Fatiguing Exercise ◽  
Exercise Induced ◽  
Male Subjects

This study examined the effect of epinephrine on glucose disposal during moderate exercise when glycogenolytic flux was limited by low preexercise skeletal muscle glycogen availability. Six male subjects cycled for 40 min at 59 ± 1% peak pulmonary O2 uptake on two occasions, either without (CON) or with (EPI) epinephrine infusion starting after 20 min of exercise. On the day before each experimental trial, subjects completed fatiguing exercise and then maintained a low carbohydrate diet to lower muscle glycogen. Muscle samples were obtained after 20 and 40 min of exercise, and glucose kinetics were measured using [6,6-2H]glucose. Exercise increased plasma epinephrine above resting concentrations in both trials, and plasma epinephrine was higher ( P < 0.05) during the final 20 min in EPI compared with CON. Muscle glycogen levels were low after 20 min of exercise (CON, 117 ± 25; EPI, 122 ± 20 mmol/kg dry matter), and net muscle glycogen breakdown and muscle glucose 6-phosphate levels during the subsequent 20 min of exercise were unaffected by epinephrine infusion. Plasma glucose increased with epinephrine infusion (i.e., 20–40 min), and this was due to a decrease in glucose disposal (Rd) (40 min: CON, 33.8 ± 3; EPI, 20.9 ± 4.9 μmol · kg−1 · min−1, P < 0.05), because the exercise-induced rise in glucose rate of appearance was similar in the trials. These results show that glucose Rd during exercise is reduced by elevated plasma epinephrine, even when muscle glycogen availability and utilization are low. This suggests that the effect of epinephrine does not appear to be mediated by increased glucose 6-phosphate, secondary to enhanced muscle glycogenolysis, but may be linked to a direct effect of epinephrine on sarcolemmal glucose transport.

Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy

1997 ◽  
Vol 273 (5) ◽  
pp. F777-F782 ◽  
Author(s):  
Arlene B. Chapman ◽  
Stacy Zamudio ◽  
Whitney Woodmansee ◽  
Aicha Merouani ◽  
Fritz Osorio ◽  
...  
Keyword(s):  
Glomerular Filtration Rate ◽  
Menstrual Cycle ◽  
Glomerular Filtration ◽  
Early Pregnancy ◽  
Plasma Flow ◽  
Luteal Phase ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Hemodynamic Changes ◽  
Midluteal Phase

Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 ± 2.0 vs. midluteal of 75.4 ± 2.3 mmHg, P< 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3′,5′-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes.

Role of Cyclic AMP in the Natriuresis of Extracellular Fluid Volume Expansion in the Dog

1977 ◽  
Vol 53 (6) ◽  
pp. 563-571
Author(s):  
R. M. Friedler ◽  
C. Descoeudres ◽  
K. Kurokawa ◽  
W.-J. Kreusser ◽  
S. G. Massry
Keyword(s):  
Body Weight ◽  
Cyclic Amp ◽  
Renal Vein ◽  
Volume Expansion ◽  
Renal Plasma Flow ◽  
Extracellular Volume ◽  
Extracellular Fluid ◽  
Net Production ◽  
Extracellular Volume Expansion

1. The effect of extracellular volume expansion (ECVE) on renal production of cyclic AMP was evaluated in 19 thyroparathyroidectomized dogs. ECVE was produced by the infusion of Ringer bicarbonate solution at a rate of 2 ml min−1 kg−1 body weight; cyclic AMP was measured in plasma obtained from the aorta and renal vein and in the urine. 2. During the natriuresis of ECVE urinary excretion of cyclic AMP, the clearance of cyclic AMP, net nephrogenous cyclic AMP added both to urine and to the renal vein and hence total nephrogenous cyclic AMP increased significantly. 3. This rise in net production of cyclic AMP and a significant natriuresis by the kidney persisted for 60–90 min after discontinuation of active ECVE and return of renal plasma flow to normal. 4. The results support the notion that an increase in the production of cyclic AMP by the kidney may play a role in the natriuresis of ECVE.

Prostaglandin E2 but not F2 alpha restores the natriuretic response to acetylcholine in indomethacin-treated dogs

1984 ◽  
Vol 247 (1) ◽  
pp. F185-F191
Author(s):  
J. C. Yun ◽  
J. R. Gill ◽  
S. S. Ho ◽  
G. D. Kelly ◽  
H. R. Keiser
Keyword(s):  
Glomerular Filtration Rate ◽  
Plasma Flow ◽  
Filtration Rate ◽  
Renal Plasma Flow ◽  
Progressive Increase ◽  
Prostaglandin Synthesis ◽  
Urinary Flow ◽  
Arterial Infusion ◽  
Secretory Rate

Renal arterial infusion of acetylcholine (ACh) (40 micrograms/min) produces a natriuresis, diuresis, and an increase in renal plasma flow (RPF) without a change in glomerular filtration rate (GFR) or renin secretory rate (RSR). The present study was designed to examine the role of prostaglandins in this natriuretic response to ACh. In dogs pretreated with indomethacin (Indo) (5 mg/kg, i.v.), an inhibitor of prostaglandin synthesis, renal arterial infusion of ACh produced an increase and then a decline in urinary flow and sodium excretion accompanied by a progressive fall in GFR and RPF and a progressive increase in RSR. Renal arterial infusion of PGE2 (1.9 micrograms/min) but not PGF2 alpha (1.9 micrograms/min) before and during the infusion of ACh restored the diuretic and natriuretic response to ACh in Indo-treated dogs. Renal arterial infusion of bradykinin (BK) (3 micrograms/min) in Indo-treated dogs produced a diuresis and natriuresis similar to that produced by PGE2; renal arterial infusion of BK, however, did not restore the diuretic and natriuretic response to ACh in Indo-treated dogs. The data suggest that Indo shortens the diuretic and natriuretic response to ACh by inhibiting synthesis of prostaglandins, possibly PGE but not PGF. The data further suggest that PGE2 restores the diuretic and natriuretic response to ACh in Indo-treated dogs through a specific action rather than by its action as a renal vasodilator.

Glomerular hemodynamics in aortocaval fistula rats: role of renin-angiotensin system

1993 ◽  
Vol 264 (4) ◽  
pp. R681-R686 ◽  
Author(s):  
T. Nishikimi ◽  
E. D. Frohlich
Keyword(s):  
Plasma Flow ◽  
Diastolic Pressure ◽  
Renal Plasma Flow ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Angiotensin System ◽  
Av Fistula ◽  
Renin Angiotensin ◽  
Single Nephron

To investigate intrarenal hemodynamics of aortocaval, arteriovenous (AV)-fistula rats and the effect of angiotensin-converting-enzyme (ACE) inhibition, micropuncture studies were obtained before and after administration of quinapril (100 micrograms.kg-1 x min-1), an ACE inhibitor. AV fistula produced by needle multipuncture was characterized by elevated left ventricular end-diastolic pressure (LVEDP), lower mean arterial pressure, and increased left and right ventricular weights. Effective renal plasma flow was lower in AV-fistula rats, and single-nephron glomerular filtration rate (SNGFR) and plasma flow (SNPF) were reduced. Single-nephron filtration faction (SNFF), stop-flow pressure, and glomerular pressure (PG) were increased. The lower SNGFR and SNPF and higher PG and SNFF were associated with higher afferent and efferent arteriolar resistances (RA and RE) and lower ultrafiltration coefficient (Kf). LVEDP correlated positively with with RA, RE, and SNFF (all P < 0.01) and negatively with SNGFR (P < 0.05) and SNPF (P < 0.01). After quinapril these variables returned toward normal. Thus this method for producing AV fistula was useful in creating mild and moderately severe cardiac failure (CHF). Intrarenal hemodynamics of AV were characterized by increased PG and SNFF and lower SNGFR and SNPF associated with increased RA and RE and lower Kf and SNPF correlated and with severity of CHF. Restoration of intrarenal hemodynamics to or toward normal with quinapril supports an important pathophysiological role of renin-angiotensin system in this CHF.

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