Increased spillover of dopa into arterial blood during dietary salt loading

1990 ◽  
Vol 78 (4) ◽  
pp. 423-429 ◽  
Author(s):  
Ehud Grossman ◽  
Aaron Hoffman ◽  
Peter C. Chang ◽  
Harry R. Keiser ◽  
David S. Goldstein
Keyword(s):  
Steady State ◽  
Urinary Excretion ◽  
Renal Denervation ◽  
Renal Nerves ◽  
Dietary Salt ◽  
Rat Strains ◽  
Salt Loading ◽  
Arterial Blood ◽  
Daily Excretion ◽  
Excretion Rates

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys. 2. Dopa spillover was calculated from the steady-state clearance of intravenously infused l-[3H]dopa and arterial levels of endogenous dopa. 3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses. 4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion. 5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.

Renal nerves and postprandial renal excretion in the conscious monkey

1991 ◽  
Vol 261 (5) ◽  
pp. R1197-R1203 ◽  
Author(s):  
T. V. Peterson ◽  
B. A. Benjamin ◽  
N. L. Hurst ◽  
C. G. Euler
Keyword(s):  
Urinary Excretion ◽  
Nonhuman Primate ◽  
Nasogastric Tube ◽  
Sodium Excretion ◽  
Renal Denervation ◽  
Renal Excretion ◽  
Renal Nerves ◽  
Electrolyte Excretion ◽  
Macaque Monkeys ◽  
High Sodium

Experiments were performed in conscious macaque monkeys to determine if the renal nerves are important in mediating postprandial increases in renal fluid-electrolyte excretion in this species. Monkeys were given a high-sodium meal via a nasogastric tube. Consecutive 10-min urine samples were taken during the 30-min time of meal administration and then 180 min postprandially. The experiment was performed both before and 10-14 days after each animal underwent renal denervation. Diuresis and natriuresis occurred under both renal-innervated and -denervated conditions. However, the amounts of urine and sodium excreted were less after renal denervation. For the total 210 min of measurements obtained after the meal was started, cumulative urine output was 95.0 +/- 26.4 ml and sodium excretion 7.18 +/- 1.74 meq in innervated kidneys vs. 56.7 +/- 7.0 ml (a 40% decrease; P less than 0.005) and 4.84 +/- 0.99 meq (a 33% decrease; P less than 0.01) after denervation. These results demonstrate that the renal nerves are important in the nonhuman primate for eliciting the postprandial changes in urinary excretion secondary to intake of a high-sodium meal.

Effects of renal denervation on renal responses to hypoxemia in fetal lambs

1986 ◽  
Vol 250 (2) ◽  
pp. F294-F301 ◽  
Author(s):  
J. E. Robillard ◽  
K. T. Nakamura ◽  
G. F. DiBona
Keyword(s):  
Renal Function ◽  
Renal Denervation ◽  
Renal Hemodynamics ◽  
Significant Rise ◽  
Renal Nerves ◽  
Base Line ◽  
Urinary Flow ◽  
Renal Vasoconstriction ◽  
Physiological Conditions ◽  
Arterial Blood

The role of renal nerves in mediating renal hemodynamics and renal function during normal physiological conditions and following moderate hypoxemia was studied in chronically catheterized fetal lambs (125-141 days of gestation) following unilateral renal denervation. Base-line values for renal blood flow (RBF), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow rate (UFR), urinary electrolyte (Na+, K+, and Cl-) excretion rate, and urine osmolality (Uosm) were similar in both intact and denervated kidneys. Hypoxemia was associated with a significant rise in mean arterial blood pressure and a significant decrease in heart rate. Hypoxemia produced a similar decrease in GFR and similar increases in urinary Na+ and Cl- excretion rates in both intact and denervated kidneys. However, the effect of hypoxemia on renal hemodynamics differed between intact and denervated kidneys. Hypoxemia produced a continuous and progressive decrease in RBF and increase in RVR in the intact kidney. On the other hand, renal denervation was associated with an early renal vasodilation and attenuated the reduction in RBF and the rise in RVR during hypoxemia; this early renal vasodilation was blunted following prostaglandin synthesis inhibition. Taken together, these results suggest that fetal renal denervation is not associated with significant changes in renal hemodynamics or renal function during normal physiological conditions but that renal denervation partially inhibited the renal vasoconstriction associated with fetal hypoxemia. Finally, it was found that endogenous prostaglandins counteract the renal vasoconstriction associated with fetal hypoxemia.

Renal hemodynamic changes during serial seizures in rats

1991 ◽  
Vol 261 (5) ◽  
pp. H1508-H1513
Author(s):  
R. M. Zweifler ◽  
E. M. Slaven ◽  
L. L. Rihn ◽  
J. C. Magee ◽  
N. R. Kreisman
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Status Epilepticus ◽  
Mean Arterial Blood Pressure ◽  
Renal Denervation ◽  
Adrenal Glands ◽  
Renal Nerves ◽  
Hemodynamic Changes ◽  
Arterial Blood ◽  
Early Seizures

Renal blood flow (RBF) and mean arterial blood pressure (MABP) were measured during serially induced seizures in anesthetized paralyzed rats to investigate possible alterations in hemodynamic responses during experimental status epilepticus. During initial seizures, MABP increased from 143 to 193 mmHg, and RBF decreased from 4.8 to 1.5 ml/min. In contrast, MABP fell from 124 to 100 mmHg and RBF dropped from 3.6 to 2.8 ml/min during late seizures. The large decreases in RBF during initial seizures were blocked by renal denervation or bilateral adrenalectomy. During the period of late seizures, both the increase in MABP and the decrease in RBF in response to intravenous boluses of norepinephrine fell to 55% of the preseizure value. Our data indicate that the marked decreases in RBF during early seizures can be mediated by either the renal nerves or the adrenal glands. Furthermore, decreased sensitivity of the vasculature to norepinephrine likely contributes to the diminution of both MABP and RBF responses during later seizures.

Renal denervation supersensitivity revisited

1998 ◽  
Vol 275 (4) ◽  
pp. R1239-R1246 ◽  
Author(s):  
Thomas E. Lohmeier ◽  
Glenn A. Reinhart ◽  
H. Leland Mizelle ◽  
Maohao Han ◽  
Mark M. Dean
Keyword(s):  
Plasma Levels ◽  
Renal Denervation ◽  
Plasma Concentrations ◽  
Urinary Sodium ◽  
Renal Nerves ◽  
Potassium Excretion ◽  
Denervation Supersensitivity ◽  
Chronic Infusion ◽  
Excretion Rates ◽  
Sodium And Potassium

To determine whether the chronically denervated kidney is supersensitive to either physiological or pathophysiological plasma levels of norepinephrine (NE), studies were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated and innervated kidneys. Plasma NE concentration was increased by chronic infusion of NE (4–5 days) at rates of 25, 100, and 200 ng ⋅ kg−1 ⋅ min−1. Twenty-four-hour control values for mean arterial pressure (MAP), plasma NE concentration, and ratios for urinary sodium and potassium excretion from denervated and innervated kidneys (Den/Inn) were 94 ± 4 mmHg, 145 ± 24 pg/ml, 1.05 ± 0.05, and 0.97 ± 0.07, respectively. With infusions of NE producing plasma levels of NE of up to ∼3,000 pg/ml or plasma concentrations of NE at least threefold greater than present under most pathophysiological conditions and during acute activation of the sympathetic nervous system, there were no significant long-term changes in MAP or relative excretion rates of sodium and potassium from denervated and innervated kidneys. In marked contrast, pharmacological plasma levels of NE (∼7,000 pg/ml) produced chronic increases in MAP (to 116 ± 2% of control) and sustained reductions in Den/Inn for urinary sodium and potassium excretion to 57 ± 4 and 68 ± 5% of control, respectively, indicating a lower excretion rate of these electrolytes from denervated vs. innervated kidneys. We conclude that the chronically denervated kidney does not exhibit an exaggerated antinatriuretic response to either physiological or pathophysiological levels of circulating NE. It is therefore unlikely that renal denervation supersensitivity is a confounding issue in studies employing chronic renal denervation to elucidate the role of the renal nerves in the regulation of sodium excretion.

Derivation of Urinary Dopamine from Plasma Dihydroxyphenylalanine in Humans

1993 ◽  
Vol 84 (5) ◽  
pp. 549-557 ◽  
Author(s):  
Efrat Wolfovitz ◽  
Ehud Grossman ◽  
Carol J. Folio ◽  
Harry R. Keiser ◽  
Irwin J. Kopin ◽  
...  
Keyword(s):  
Urinary Excretion ◽  
Laboratory Animals ◽  
Dietary Salt ◽  
Salt Loading ◽  
Renal Uptake ◽  
Dihydroxyphenylacetic Acid ◽  
Endogenous Dopamine ◽  
Urinary Dopamine ◽  
Arterial Plasma ◽  
A Minor

1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spillover) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 μg min−1 kg−1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenylacetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08 ± (SEM) 0.01 to 0.14 ± 0.03 nmol/min, t = 2.80, P <0.02] and dopamine (from 1.03 ± 0.19 to 1.30 ± 0.28 nmol/min, t = 2.35, P <0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged. 4. Renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endogenous dihydroxyphenylacetic acid. 5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopamine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt loading.

EVIDENCE FOR EXTRATUMOURAL STORAGE OF CATECHOLAMINES IN PHEOCHROMOCYTOMA PATIENTS

1978 ◽  
Vol 87 (3) ◽  
pp. 589-595 ◽  
Author(s):  
J. H. Hengstmann ◽  
H. J. Dengler
Keyword(s):  
Urinary Excretion ◽  
Sympathetic Nerve ◽  
Surgical Removal ◽  
Catecholamine Content ◽  
Female Patients ◽  
Cumulative Urinary Excretion ◽  
Daily Excretion ◽  
Hypertensive Crises ◽  
Excretion Rates ◽  
Vanilmandelic Acid

ABSTRACT Following the removal of a pheochromocytoma in three female patients the daily excretion of catecholamines and their metabolites was still considerably elevated for about one week. The excretion rates declined during this period with half-lives of 1.8 to 10.9 days for catecholamines and 2.1 to 4.7 days for metanephrines, vanilmandelic acid, and vanilglycol. The cumulative urinary excretion of catecholamines and their metabolites following surgical removal of the tumour was nearly as high as the catecholamine content of the pheochromocytomas. This large amount of catecholamines must have been located outside the tumour, most probably within the sympathetic nerve, where it is subject to release following physiological stimuli. Furthermore, this fact may provide an explanation for hypertensive crises in pheochromocytoma patients.

Effects of urea on the in vitro production of prostaglandins and on urinary excretion in Brattleboro rats

1989 ◽  
Vol 120 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Eigil Bojesen ◽  
Inge N. Bojesen
Keyword(s):  
Steady State ◽  
Urinary Excretion ◽  
Urea Concentration ◽  
Brattleboro Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Urine Formation ◽  
Excretion Rates

Abstract. Brattleboro rats with hereditary diabetes insipidus make it possible to investigate effects of the urea concentration on the in vitro and in vivo production of prostaglandins E2 and F2α (PGE2 and PGF2α) by the renal papilla independently of any vasopressin effects. The rates of prostaglandin production in vitro are increasing between 100 and 1030 mmol/l urea and decreasing above 1030 mmol/l. The ratio PGE2/PGF2α remains constant at about 4. Normally hydrated and 24 h water-deprived animals in steady state of urine formation were compared in vivo. Urine osmolality increased from 167 ± 6 (N = 5) to 1113 ± 35 (N = 15) mosmol/kg water and papillary urea concentration from 50 ± 7 to 304 ± 19 mmol/l after water deprivation. Urinary excretion rates of PGF2α increased from 0.83 ± 0.12 to 3.80 ± 0.37 ng/h. The excretion of PGE2 was unaffected. PGE2 + PGF2α excretion rates increased from 1.62 ± 0.25 to 4.61 ± 0.42 ng/h. These values are in accordance with values predicted from work with Sprague-Dawley rats. Together with previously published data on Sprague-Dawley rats these results indicate that variations of prostaglandin production in the conscious rat in steady state of urine formation can be accounted for by variations of plasma vasopressin and of papillary urea concentration. Variations in the excretion fraction are due to other causes.

Renal nerves and nNOS: roles in natriuresis of acute isovolumetric sodium loading in conscious rats

2008 ◽  
Vol 294 (4) ◽  
pp. R1130-R1139 ◽  
Author(s):  
Elżbieta Kompanowska-Jezierska ◽  
Helle Wolff ◽  
Marta Kuczeriszka ◽  
Jan B. Gramsbergen ◽  
Agnieszka Walkowska ◽  
...  
Keyword(s):  
Renal Denervation ◽  
Plasma Renin ◽  
Renin Secretion ◽  
Sodium Balance ◽  
Renal Nerves ◽  
Body Volume ◽  
Hypertonic Solution ◽  
Arterial Blood ◽  
Sodium Loading ◽  
Nnos Inhibition

It was hypothesized that renal sympathetic nerve activity (RSNA) and neuronal nitric oxide synthase (nNOS) are involved in the acute inhibition of renin secretion and the natriuresis following slow NaCl loading (NaLoad) and that RSNA participates in the regulation of arterial blood pressure (MABP). This was tested by NaLoad after chronic renal denervation with and without inhibition of nNOS by S-methyl-thiocitrulline (SMTC). In addition, the acute effects of renal denervation on MABP and sodium balance were assessed. Rats were investigated in the conscious, catheterized state, in metabolic cages, and acutely during anesthesia. NaLoad was performed over 2 h by intravenous infusion of hypertonic solution (50 μmol·min−1·kg body mass−1) at constant body volume conditions. SMTC was coinfused in amounts (20 μg·min−1·kg−1) reported to selectively inhibit nNOS. Directly measured MABPs of acutely and chronically denervated rats were less than control (15% and 9%, respectively, P < 0.005). Plasma renin concentration (PRC) was reduced by renal denervation (14.5 ± 0.2 vs. 19.3 ± 1.3 mIU/l, P < 0.005) and by nNOS inhibition (12.4 ± 2.3 vs. 19.6 ± 1.6 mlU/l, P < 0.005). NaLoad reduced PRC ( P < 0.05) and elevated MABP modestly ( P < 0.05) and increased sodium excretion six-fold, irrespective of renal denervation and SMTC. The metabolic data demonstrated that renal denervation lowered sodium balance during the first days after denervation ( P < 0.001). These data show that renal denervation decreases MABP and renin secretion. However, neither renal denervation nor nNOS inhibition affects either the renin down-regulation or the natriuretic response to acute sodium loading. Acute sodium-driven renin regulation seems independent of RSNA and nNOS under the present conditions.

Urinary excretion of dihydroxyphenylalanine and dopamine during alterations of dietary salt intake in humans

1989 ◽  
Vol 76 (5) ◽  
pp. 517-522 ◽  
Author(s):  
David S. Goldstein ◽  
Robin Stull ◽  
Graeme Eisenhofer ◽  
John R. Gill
Keyword(s):  
Urinary Excretion ◽  
Salt Intake ◽  
Sodium Intake ◽  
Sodium Balance ◽  
Dietary Salt ◽  
Proximal Tubular Cells ◽  
Salt Loading ◽  
Dietary Salt Intake ◽  
Tubular Cells ◽  
Proximal Tubular

1. Urinary excretion of dopamine (DA) increases during dietary salt loading. The majority of urinary DA is derived from circulating dihydroxyphenylalanine (dopa). Whether the increase in urinary DA excretion during salt loading results from increased efficiency of uptake of dopa by proximal tubular cells of the kidney, facilitation of intracellular conversion of dopa to DA, or increased delivery of dopa to tubular uptake sites, has been unknown. 2. In 10 inpatient normal volunteers on a constant diet, daily excretion of dopa and DA was assessed during normal sodium intake (109 mmol/day) for 1 week, low sodium intake (9 mmol/day) for 1 week and high sodium intake (249 mmol/day) for 1 week. 3. Urinary DA excretion exceeded urinary dopa excretion by about tenfold, and the excretion of both DA and dopa increased by about twofold between the low and high salt diets, with similar proportionate changes. Plasma dopa was unchanged by dietary salt manipulation. 4. The results indicate that increases in urinary DA excretion during dietary salt loading can be accounted for by increased delivery of dopa to sites of uptake by proximal tubular cells. Since dopa is released into the bloodstream by sympathetic nerve endings and by the brain, and since interference with decarboxylation of dopa attenuates natriuretic responses, dopa may function indirectly as a neurohormone involved in homoeostatic regulation of sodium balance.

Selective efferent chemical sympathectomy of rat kidneys

1985 ◽  
Vol 249 (4) ◽  
pp. R496-R501
Author(s):  
L. M. LeNoble ◽  
R. W. Lappe ◽  
M. J. Brody ◽  
H. A. Struyker Boudier ◽  
J. F. Smits
Keyword(s):  
Blood Pressure ◽  
Renal Denervation ◽  
Left Kidney ◽  
Posterior Hypothalamus ◽  
Renal Nerves ◽  
Chemical Sympathectomy ◽  
Arterial Blood ◽  
6 Hydroxydopamine ◽  
The Right ◽  
And Control

Surgical denervation of kidneys results in interruption of both afferent and efferent renal nerves. We attempted selective efferent renal denervation in rats by slow infusions of 6-hydroxydopamine (6-OHDA) into the right renal artery. Integrity of efferent renal nerves was assessed by chemical and physiological methods and by measuring responses of mean arterial blood pressure (MAP) and heart rate (HR) to intrarenal (ir) infusion of bradykinin in conscious rats. Results were compared with those in surgically denervated and ir saline-infused rats. Surgical denervation of left kidney reduced renal norepinephrine (NE) to 58 and 14% of control levels at 1 and 7 days, respectively, after surgery. Increase in left renal resistance during posterior hypothalamus (PH) stimulation was only 70 +/- 28% (n = 5) compared with 289 +/- 69% (n = 6) in control animals. Response in opposite kidney was unchanged. Although 0.1 mg 6-OHDA ir caused considerable reduction of NE levels in both kidneys, responses to PH stimulation were unchanged. 6-OHDA (1 mg) reduced NE levels in infused and control kidney and atria. Functional evidence for denervation was only obtained in the kidney infused with 6-OHDA. Responses of MAP and HR to ir bradykinin were unchanged 7 days after 1 mg 6-OHDA. The data suggest that ir 6-OHDA results in functional efferent sympathectomy without affecting afferent renal nerves.

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