Changes In Sodium Excretion Research Articles

Lack of effect of short-term changes in sodium intake on blood pressure in adolescent schoolchildren

The relationship between sodium intake and blood pressure in adolescents was examined in a dietary intervention study. One hundred schoolchildren aged 11-14 years and representing the top, middle and bottom deciles of the blood pressure range completed a crossover protocol requiring them to raise and lower their sodium intake for alternate periods of 4 weeks. Blood pressure and urinary sodium excretion were assessed weekly and diet diaries were recorded at the end of each 4-week diet period. Diet-diary analysis confirmed that sodium intake was selectively affected by the intervention. Estimates of average urinary sodium excretion at the end of each diet period differed by more than 80 mmol/day. However, there was no significant change of either systolic or diastolic blood pressure, measured supine in the whole study group, in either sex or in any of the sub-groups, even in those children representing the highest blood pressure decile. Furthermore, the blood pressure changes seen in individuals during the crossover did not correlate with their changes in sodium excretion. This lack of effect of sodium on blood pressure is consistent with other dietary intervention studies in children and supports the hypothesis that the sodium sensitivity of blood pressure is age-related. We conclude that dietary sodium restriction alone has little potential for lowering blood pressure at an early age, even in children with higher than average blood pressure.

VASCULAR ACTIONS OF ENDOTHELIN IN THE RABBIT KIDNEY

1. The effect of two doses of endothelin, 10 and 50 ng/kg per min, i.v., on glomerular filtration rate (GFR), tubular stop flow pressure and pre- and post-glomerular vascular resistance have been studied in anaesthetized rabbits. 2. Blood pressure did not change significantly in response to 10 ng/kg per min endothelin or vehicle infusion, but rose steadily during infusion of 50 ng/kg per min endothelin, increasing 11.8 +/- 2.7 mmHg by 90 min of infusion. 3. Glomerular filtration fraction (3H-inulin extraction ratio) rose and remained elevated throughout the endothelin infusion at 50 ng/kg per min. GFR did not change significantly until 70-90 min of the infusion (50 ng/kg per min) when it decreased by about 35%. No significant changes were seen at 10 ng/kg per min endothelin. 4. Sodium excretion rate rose in response to the lower dose, due to an increase in fractional sodium excretion. No changes in sodium excretion were seen at the higher dose of endothelin. 5. Glomerular capillary pressure rose significantly in response to endothelin infusion (50 ng/kg per min). 6. Renal blood flow fell progressively in response to endothelin (50 ng/kg per min), to about one-third of the pre-infusion value. 7. Renal vascular resistance increased progressively with both doses of endothelin, by about 35% at 10 ng/kg per min and about 400% at 50 ng/kg per min after 70-90 min. Preglomerular resistance increased from 1.0 +/- 0.1 to 5.0 +/- 1.9 mmHg/mL per min in response to endothelin 50 ng/kg per min. Postglomerular resistance rose from 1.0 +/- 0.1 to 5.6 +/- 2.17 mmHg/mL per min. 8. Thus endothelin infusion caused progressive renal vasoconstriction with similar magnitude increases in both pre- and postglomerular vessels. The vasoconstriction of the kidney caused by endothelin occurred at a dose which did not effect systemic blood pressure.

Serial natriuretic response to atrial peptide in preascitic bile duct ligated dogs

We determined if nine precirrhotic unanaesthetized dogs with chronic bile duct ligation (CBDL) responded uniformly to atrial natriuretic peptide (ANF) by infusing this peptide sequentially over 8-12 weeks at 175 ng.kg-1.min-1 and observing the natriuretic response. ANF was administered every 2 weeks post-CBDL until the 8th week and given again during the cirrhotic phase with ascites present (10-12 weeks post-CBDL). Sodium balance studies were conducted at similar time intervals. During the control period and at weeks, 2, 6, and 8 post-CBDL all dogs responded to ANF with a significant change in sodium excretion (delta UNaV, 50-240 mu equiv./min). At these times, all dogs were in sodium balance. At week 4 and during the ascitic period, heterogeneity of response to ANF was observed. In the former interval, five dogs responded (delta UNaV,75-230 mu equiv./min) and four did not, while in the latter interval, five dogs responded (delta UNaV, 50-240 mu equiv./min) and three did not (one dog died). In both time periods, there was severe urinary sodium retention (daily UNaV, 11 +/- 3 and 2 +/- 1 mequiv./day, respectively) while the dogs were ingesting 45 mequiv.Na+/day. The heterogeneity of natriuretic response was not correlated to plasma immunoreactive ANF, renin, or aldosterone levels. Plasma volume was significantly expanded from control during both intervals. We conclude that there is transient sodium retention during the 4th week post-CBDL, and that this period is associated with the heterogeneity of natriuretic response to ANF, despite the absence of ascites or edema.

Long term reduction in sodium balance: possible additional mechanism whereby nifedipine lowers blood pressure.

To assess the changes in sodium excretion and sodium balance after withdrawal of long term nifedipine. Single blind, placebo controlled study in patients receiving fixed sodium and potassium intakes. Blood pressure unit of a teaching hospital in south London. Eight patients with mild to moderate uncomplicated essential hypertension who had been taking nifedipine 20 mg twice daily for at least six weeks. Withdrawal of nifedipine and replacement with matching placebo for one week. Urinary sodium excretion and cumulative sodium balance, body weight, plasma atrial natriuretic peptide concentrations, plasma renin activity and aldosterone concentrations, and blood pressure. During nifedipine withdrawal there was a significant reduction in urinary sodium excretion (day 1: -62.7 mmol/24 h; 95% confidence interval -90.3 to -35.0) and each patient retained a mean of 146 (SEM 26) mmol sodium over the week of replacement with placebo. Body weight and plasma atrial natriuretic peptide concentrations increased during the placebo period and seemed to be associated with the amount of sodium retained. Systolic blood pressure rose from 157 (9) to 165 (9) mmHg (95% confidence interval of difference -7.1 to 22.1) when nifedipine was replaced with matching placebo, and the rise seemed to be related to the amount of sodium that was retained. Nifedipine causes a long term reduction in sodium balance in patients with essential hypertension. This long term effect may contribute to the mechanism whereby nifedipine lowers blood pressure.

Dopaminergic Modulation of Acute Renal Effects of Nicardipine

In order to investigate whether dopamine receptors are involved in the acute natriuretic effects of calcium channel blockade, experiments were carried out in humans with uncomplicated essential hypertension. In 8 hypertensives 5 mg intravenous nicardipine produced a large decrease in blood pressure and renal vascular resistance, a slight but significant increase in glomerular filtration rate (GFR) and marked natriuresis. When a second identical experiment was performed in the same subjects with the addition of 10 mg metoclopramide as dopamine blocker, changes in sodium excretion and vascular resistance were the same, but GFR did not increase during nicardipine. In a second set of experiments (n = 5) the same design was used, but nicardipine was infused at a dose of 0.01 mg/kg, ie, seven times less than in previous experiments. Under these conditions, blood pressure, renal vascular resistance and GFR did not change, but significant natriuresis occurred. Natriuresis was almost completely prevented by metoclopramide. In 5 additional hypertensives, metoclopramide alone was infused and 0.01 mg/kg nicardipine was added to the infusion. No change in any parameter was observed. Our findings suggest that the dopaminergic system participates in maintaining or increasing GFR during blood pressure reduction by calcium antagonists, although renal vasodilation and natriuresis are largely independent of dopamine receptor activity. In addition, when low doses of calcium antagonists produce natriuresis in the absence of renal or systemic hemodynamic changes (direct tubular effect), dopamine blockade is able to blunt this effect. This indicates a modulation by dopaminergic receptors of the direct tubular action of calcium antagonists.

Control of arterial pressure and renal function during chronic renin inhibition

The aim of this study was to determine whether the renin inhibitor CP-71362 (Pfizer Central Research, Groton, Connecticut, USA) is capable of inducing sustained reductions in arterial pressure in sodium-depleted dogs and to examine the changes in renal function associated with chronic renin inhibition. In addition, we also examined the chronic effects on renal function and blood pressure of the angiotensin converting enzyme (ACE) inhibitor enalaprilat. Infusion of CP-71362 (1.1 micrograms/kg per min, intravenously) for 7 days decreased mean arterial pressure from 87 +/- 3 to 75 +/- 2 mmHg, while causing no significant changes in sodium excretion, the glomerular filtration rate, or effective renal plasma flow. Plasma renin activity was suppressed to undetectable levels throughout the 7 days of CP-71362 infusion. Infusion of enalaprilat (4 mg/kg per day) for 7 days in sodium-depleted dogs decreased mean arterial pressure (from 85 +/- 2 to 64 +/- 3 mmHg) and renal vascular resistance, and increased effective renal plasma flow and sodium excretion, but caused no significant changes in the glomerular filtration rate. Thus CP-71362 is a potent inhibitor of dog plasma renin, and we observed no waning of this inhibitory effect of CP-71362's hypotensive actions over 7 days. The mechanisms responsible for the differences in the blood pressure and renal responses to CP-71362 and ACE inhibition are not clear, but may be dose-related or due to differences in the distribution of these compounds to various tissues, including the kidney.

Dissociation of renal interstitial hydrostatic pressure and natriuresis of atrial natriuretic factor

The objective of these experiments was to test the hypothesis that renal interstitial hydrostatic pressure (RIHP) plays an important role in the natriuretic effect of atrial natriuretic factor (ANF) in anesthetized Wistar rats. Three groups of male Wistar rats were used in this study. Two groups were infused with different doses of ANF, and the third group was a time control. In all groups, one kidney was acutely decapsulated, and the contralateral kidney was used as control. Renal decapsulation was used to control RIHP. In one group, 3 micrograms.kg-1.h-1 of synthetic ANF were infused intravenously (iv) and produced a plasma level of ANF (PANF) of 810 +/- 186.5 pg/ml. This pharmacological dose of ANF produced a significant increase in RIHP of the control kidney from 9.5 +/- 0.8 to 11.1 +/- 1.3 mmHg (P less than 0.05) but not in the decapsulated kidney [from 7.1 +/- 0.6 to 8.1 +/- 0.9 mmHg, not significant (NS)]. However, the changes in fractional excretion of sodium (FENa) and urine flow rate (V) as a result of ANF infusion were similar in both kidneys. In the decapsulated kidney, FENa and V increased by 1.53 +/- 0.41% and 26.21 +/- 5.98 microliters/min, respectively, from control to ANF infusion periods. In the control kidney, FENa and V increased by 1.60 +/- 0.28% and 31.61 +/- 5.87 microliters/min, respectively, from control to ANF infusion periods. In the second group, 1 microgram.kg-1.h-1 iv of synthetic ANF was infused and produced 165.2 +/- 29.3 pg/ml of PANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium Excretion and Hyperfiltration during Glucose Infusion in Man

The relations between renal hemodynamics (Inutest, CPAH) and sodium excretion were studied in 7 nondiabetics in whom a similar expansion was induced (1) with a 3-hour 5% glucose infusion and (2) with a 0.9% saline load. With both infusions the body weight increased, hematocrit fell, and the plasma renin activity was suppressed. During glucose infusion, blood glucose rose from 3.9 mmol/l to a plateau of around 13 mmol/l; glycosuria was absent during the 1st h, then appeared and stabilized during the following 2h. Glucose infusion caused a progressive increase in glomerular filtration rate and in renal blood flow in both absence and presence of glycosuria, without significant changes in sodium excretion despite volume expansion and increase of filtered sodium load. When saline was infused, there was a sustained increase of fractional sodium excretion, and no hemodynamic modifications were observed. We suggest that a primary glucose-induced metabolic stimulation of sodium reabsorption may play a role in the genesis of glucose-induced hyperfiltration.

Potentiation of calcitonin by corticosteroids during the treatment of the hypercalcaemia of malignancy

Some patients treated for the hypercalcaemia of malignancy develop renal tubular resistance to the effects of calcitonin which is independent of concurrent changes in sodium excretion. This type of resistance can be overcome by the addition of corticosteroids. In other patients apparent renal resistance to calcitonin is a consequence of reduced sodium excretion and is unaffected by corticosteroids.

Stereoselective saluretic effect and localization of renal tubular secretion of enantiomers of S‐8666, a novel uricosuric antihypertensive diuretic

AbstractS‐8666, a newly developed antihypertensive uricosuric diuretic, possesses an asymmetric carbon and exists as a racemic mixture. The enantioselectivity of S‐8666 in natriuresis and the renal excretory mechanisms of the S‐8666 enantiomers were examined. Dose‐dependent natriuresis of the S‐(−)‐enantiomer was observed in male Sprague‐Dawley rats (3–100 mg/kg, p.o.), female Slc:ddy mice (3–300 mg/kg, p.o.) and male NIBS Japan white rabbits (1–10 mg/kg, i.v.). The R‐(+)‐enantiomer produced no significant change in sodium excretion within dose ranges of 100–200 mg/kg p.o. for rats, 3–300 mg/kg p.o. for mice, and 10 mg/kg i.v. for rabits. The (−)‐enantiomer and racemic S‐8666 showed a high‐ceiling property like that of furosemide and unlike that of trichlormethiazide. Plasma protein binding of S‐8666 was over 95% in rabbits and 73% in beagle dogs. In rabbits, both enantiomers of S‐8666 were secreted equally from the proximal tubule; however, only the (−)‐enantiomer of S‐8666 showed diuresis in a stop‐flow pattern. In beagle dogs, secretion of racemic S‐8666 occurred from the proximal tubule and could be inhibited by probenecid. The renal excretion of S‐8666 was largely the result of tubular excretion in rabbits whereas in beagle dogs, some glomerular filtration was also involved in urinary excretion. In conclusion, S‐8666 shows enantioselectivity in natriuresis. Both enantiomers of S‐8666 are excreted mostly by the organic acid transport system in the proximal tubule, but only the (−)‐enantiomer of S‐8666 induces natriuresis from the luminal side of the tubule.

Long-term effects of isradipine on blood pressure and renal function

The hemodynamic and renal effects of isradipine were investigated in 10 hypertensive patients treated for 3.5 months and in a further nine patients treated for two years. Both groups achieved significant and sustained reductions in systolic blood pressure/diastolic blood pressure (−15 percent/−12 percent and −15 percent/−20 percent, respectively; p < 0.001). Renal parameters were investigated two to three hours after the morning dose of isradipine, using a water-loading procedure. After 3.5 months of treatment, the glomerular filtration rate and renal plasma flow showed small increases (+6 percent and +9 percent, respectively, p < 0.05), whereas, after two years, these changes were no longer present (+4 percent and 0 percent). Clearance of sodium and uric acid was increased by 40 percent ( p < 0.01) and 21 percent ( p < 0.01), respectively, after 3.5 months, and by 45 percent ( p < 0.05) and 23 percent ( p < 0.01), respectively, after two years. Lithium clearance studies revealed the natriuretic effect to be located in the proximal tubule. After 3.5 months, a significant relationship was found between the blood pressure response and the change in sodium excretion, but this relationship also was no longer present after two years. In conclusion, because of a maintained blood pressure-lowering effect while preserving renal function, and sustained natriuretic and uricosuric actions, isradipine can be considered a promising agent in the long-term treatment of arterial hypertension.

Plasma concentration and renal effect of human atrial natriuretic peptide in nephrotic syndrome.

To elucidate the pathophysiological role of atrial natriuretic peptide (ANP) in nephrotic syndrome, the plasma level of ANP and renal response to exogenous human alpha-ANP (alpha-hANP) were measured in untreated adult patients with idiopathic nephrotic syndrome (NS) and compared with those of normal volunteers (NL). The plasma concentration of immunoreactive ANP (ir-ANP) in NS (112 +/- 9.8 pg/ml, n = 9, mean +/- SE) was not significantly different from that in NL (98 +/- 8.0 pg/ml, n = 13). However, a significant positive correlation was observed between the plasma ir-ANP level and blood volume in NS (r = 0.714, p less than 0.05). In an infusion study with synthetic alpha-hANP (25 to 100 ng/kg/min), the urine flow rate increased from 0.67 +/- 0.08 to 7.11 +/- 1.08 ml/min in NL (n = 5, p less than 0.01) and from 0.64 +/- 0.16 to 2.88 +/- 0.70 ml/min in NS (n = 9, p less than 0.05) and the urinary sodium excretion increased from 115 +/- 16 to 466 +/- 62 microEq/min in NL (p less than 0.01) and from 51 +/- 8 to 207 +/- 58 microEq/min in NS (p less than 0.01). The absolute and percent changes in urine flow rate and the absolute change in sodium excretion were lower in NS (p less than 0.05) than in NL. The percent change in sodium excretion in NS did not differ from that in NL. In 2 patients with high plasma ir-ANP concentrations, however, infusion of ANP induced poor sodium excretion (59 and 95 microEq/min at 100 ng/kg/min ANP infusion, respectively). Hemodynamic and renal parameters such as blood pressure, pulse rate and creatinine clearance were similarly affected in both NL and NS. We also found that the urinary excretion of protein was significantly increased in NS (p less than 0.05) during infusion of alpha-hANP. Our data suggest that the plasma level of ir-ANP is regulated by blood volume status, and that the renal responsiveness to ANP, at least in part, contributes to water and sodium retention in NS.

Continuous intragastric delivery of fenoldopam: relationship between plasma concentration and effects on renal function.

1. The pharmacodynamics of the dopamine DA1 agonist fenoldopam were examined in six healthy male volunteers after constant intragastric infusions of fenoldopam at dosages of 0, 10, 25, 50 and 75 mg h-1 for 6 h. 2. Hourly p-aminohippurate (PAH) clearance was used to assess fenoldopam induced renal plasma flow changes. Marked dose-related increases in renal plasma flow were noted with a maximal increase of 65% over baseline values of 711 ml min-1 being seen at the 75 mg h-1 rate. No changes in sodium excretion and glomerular filtration rate were observed. 3. Mean steady-state fenoldopam plasma concentrations were related to mean PAH clearance based on an Emax model (r = 0.996) with an Emax of 1350 ml min-1 and an EC50 of 6.2 ng ml-1. 4. Mean steady-state plasma concentrations of fenoldopam-7-sulphate and fenoldopam-8-sulphate failed to increase with dose but were linearly correlated to mean PAH changes (r = 0.998, r = 0.981 respectively). 5. These results support the concept of extending fenoldopam's duration of action through the development of an oral sustained delivery system.

Angiotensins II and III prevent captopril-induced renin release in the rat.

1. The effects of exogenous angiotensins II and III (50 pmol/min i.v.) on plasma renin release following captopril injection (5 mg/kg, i.v.) were studied in anaesthetized Sprague-Dawley rats, to determine whether angiotensin II blockade is the major mechanism by which captopril induces renin release. 2. Captopril produced a 12-fold increase in plasma renin concentration compared with saline-injected controls. This was completely reversed by pre-infusion of angiotensin II or III. 3. The fall in blood pressure following captopril treatment was also abolished by angiotensins II and III pre-infusion. Noradrenaline pre-infusion (200-800 ng/min, i.v.) also prevented the captopril-induced hypotension but did not alter the rise in plasma renin. 4. Ureteric ligation did not significantly reduce captopril-induced renin release suggesting that acute changes in sodium excretion or delivery of electrolyte to the macula densa were not involved in renin release. 5. These findings suggest that captopril induces renin release by inhibiting angiotensin II feedback control of renin secretion and that angiotensin III may also modulate renin release.

Frusemide pretreatment blunts the inhibition of renal tubular sodium reabsorption by ANF in man.

The effects of atrial natriuretic factor (ANF) 15 pmol/kg/min on renal function were studied in 7 normal male volunteers during maximal water diuresis. Subjects were studied in neutral salt balance either before, or after, seven days treatment with 40 mg oral frusemide. The post-frusemide state was associated with activation of the renin-angiotensin system (RAAS) and generally higher noradrenaline levels; this state was also associated with sodium retention, mainly due to enhanced distal nephron reabsorption. Without diuretic pretreatment ANF produced a natriuresis and diuresis associated with inhibition of both proximal and distal nephron sodium reabsorption. In contrast, after frusemide pretreatment, ANF caused an increase in water excretion (urinary flow rate) but no change in sodium excretion. In the post-diuretic condition ANF did not affect renal tubular handling of sodium. The enhanced tubular reabsorption of sodium post-frusemide, and the failure of ANF to suppress this, could be due to activation of the RAAS and SNS.

Lack of evidence for a cerebral sodium modulating mechanism in the monkey.

Experiments were carried out in seven conscious macaque monkeys undergoing a water diuresis to determine the effects of raising carotid blood sodium concentration on renal sodium excretion and free water clearance. On separate days each animal received an intracarotid infusion of hypertonic sodium chloride (90 Eq NaCl/kg.body wt./min) for 5 to 10 min, the same hypertonic infusion intravenously, and an intracarotid infusion of isotonic NaCl. None of the infusions produced a change in sodium excretion. However, the intracarotid hypertonic infusion produced a sustained decrease in free water excretion while the other infusion did not. Creatinine clearance was not affected by any of the infusions. The results of these experiments support the view that while the brain of the primate contains an osmotic sensing mechanism it does not contain a mechanism which modulates sodium excretion.

The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action.

Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.

Central renin-angiotensin system and the pathogenesis of DOCA-salt hypertension in rats.

The antihypertensive effect of blockade of the brain renin-angiotensin system (brain RAS) was investigated in DOCA (deoxycorticosterone acetate)-salt hypertensive rats. Continuous intracerebroventricular (ICV) administration of SQ14225 (SQ; 1.25 micrograms X 0.5 microliter-1 X h-1) for 7 days attenuated the increase in blood pressure (99 +/- 5 vs. 116 +/- 4 mmHg on the 7th day) and also reduced the elevation of blood pressure (157 +/- 7 vs. 138 +/- 6 mmHg) in these hypertensive rats. Attenuation of increasing blood pressure in the developing phase following ICV SQ treatment was accompanied by decrease of fluid intake and prevention of elevation of the plasma vasopressin. In the established phase, in addition to reduction of the plasma vasopressin and decrease of fluid intake, restoration of the impaired baroreceptor reflexes was brought about by ICV SQ treatment. These results indicate that the brain RAS strongly influences the regulation of blood pressure in DOCA-salt hypertensive rats and that its mechanism of action is closely related to changes in sodium excretion, vasopressin, and the baroreceptor reflexes.

The effect of oral digoxin on sodium excretion, renin-angiotensin-aldosterone system and blood pressure in normotensive subjects.

The effect of digoxin (0.25 mg t.d.s.) given orally for 5 days, on sodium excretion, plasma renin activity, plasma aldosterone and blood pressure has been studied in 6 normotensive subjects, on a constant sodium intake. Average serum digoxin level measured in 5 subjects on the 5th day of treatment was in the upper range of the therapeutic level (1.92 +/- 0.3 nmol/l). Red cell sodium content increased from 9.75 +/- 1.2 mmol/l of cells in the control period to 15.3 +/- 1.7 mmol/l of cells on the 5th day of digoxin treatment when measured in 4 of the 6 subjects. In spite of this evidence of inhibition of the red cell sodium pump, there was no detectable change in sodium excretion, blood pressure, plasma renin activity and aldosterone.

Effects of graded changes in reflex renal nerve activity on renal function.

The effects of reflexly produced graded increases in renal nerve activity on excretion of sodium and potassium, urinary flow, glomerular filtration rate (GFR), renal plasma flow (RPF), renin release, and renal venous norepinephrine (NE) overflow were examined in anesthetized dogs. Renal nerve activity was increased by carotid artery occlusion while renal perfusion pressure was held constant. Linear correlation was determined by plotting the percent change from control for each dependent variable vs. the percent change in mean renal nerve activity (MRNA). The percent changes from control for sodium excretion and urinary flow were negatively correlated with percent change from control in MRNA (P less than 0.01), and the percent change from control for renin release was positively correlated with percent change from control in MRNA (P less than 0.05). NE overflow was observed to increase as renal nerve activity increased. These results indicate that physiologically elicited increases in MRNA from 10 to greater than 100% are significantly correlated with changes in sodium excretion, urine flow, and renin release with little or no measurable change in GFR, RPF, or potassium excretion.