low-Na Diet Research Articles

Aldosterone-induced, amiloride-inhibitable short-circuit current in the avian ileum.

Transmural electrical potential difference, short-circuit current (Isc), and resistance were measured in vitro in the intestines of chickens. In birds maintained on a low-Na diet, there was a rise in Isc in the ileum and the colon but not in the duodenum or jejunum. A substantial portion of this Isc could be inhibited by the Na channel-blocking drug, amiloride. The low-Na diet results in elevated plasma levels of aldosterone and the effects of the diet on intestinal transport could be mimicked by administration of this hormone. The time course of the effects of these two treatments on the ileum and colon were quite different, as a much longer exposure was needed to elicit maximal effects in the ileum than in the colon, possibly due to the presence of two types of adaptation mechanisms. The responses observed may reflect an adaptation of mechanisms for increasing Na transport from the intestine. The presence of such a mechanism in the vertebrate ileum has until recently been in doubt.

Effects of sodium intake during two parities on Na status in blackface sheep.

A low-sodium diet was given to Blackface ewes over two reproductive seasons. This diet provided a total of 3-7 mmol/d except during lactation when the intake was about 11 mmol/d. Control ewes were given the same diet supplemented with sodium chloride to provide recommended levels which were about tenfold that of the experimental diet. The output of Na in urine and faeces from ewes given the low-Na diet was very low, about 3 mmol/d, from early in the experiment and continued at about this level throughout. Lambs born to low-Na ewes and given a low-Na diet similar to that of their dams during lactation, grew, after weaning, more slowly than corresponding lambs from control ewes, but at 6 months of age when six from each group were killed, tissue Na contents were only slightly lower in experimental than control lambs. Fluids and tissues obtained at the end of the second lactation from four ewes of each group that had suckled twin lambs, were analysed for Na and potassium. The Na concentration in saliva and rumen fluid of low-Na ewes was about half that of control ewes and there were corresponding increases in K: the differences were significant. Although Na concentrations for experimental ewes were generally lower than those for control ewes in the tissues analysed (liver, kidney, heart, brain and bone), the difference was significant only for the heart (P less than 0.05). Haemoglobin and packed cell volume were significantly elevated in low-Na ewes (P less than 0.01), indicating decreased body fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Handling of a sodium load by rats on a low sodium intake and frusemide.

1. Groups of rats (n = 9-10 per group) were given a medium sodium (Na) diet or a low Na diet or a low Na diet plus low or high dose frusemide in order to have their body Na in a state of surplus or deficit or neither. 2. Body Na was measured by a 22Na whole body counting method involving Na-free chow and the drinking fluid as the only source of Na (22Na-labelled NaCl). Intraperitoneal NaCl (same specific activity) loads were given and their excretion was measured by repeated measurements of body Na over the next 48 h. 3. Rats in surplus excreted more than the load; those in neither surplus nor deficit excreted more or less exactly the load (allowing for growth); those with a small deficit retained enough Na to make up most of the deficit; those with a deficit that was larger than the load retained approximately the whole load. 4. The results support the Strauss-Hollenberg concept that there is a basal body Na above which Na is excreted and below which any available Na is retained.

The rapid adjustment of renal sodium excretion to changes in dietary sodium intake in sheep

The rapidity with which the kidney alters sodium excretion (ENa) in response to changes in dietary Na was studied in Merino sheep by analyzing hourly ENa for three control days, and then for three days after a change in Na intake. On a control diet of 117 mmol Na, sheep had a pre-feeding ENa of 3.5 mmol/hr., a striking post-feeding natriuresis that began 2 hours after feeding (<0.01), peaked at 4 hrs. and then declined to pre-feeding levels 7 hrs. after feeding. When in balance on a high Na diet the feeding of a low Na meal resulted in marked depression of ENa within 4 hours after feeding. On a low Na diet, a 100 mmol Na meal resluted in an increase in ENa within 4 hours but a 50 mmol Na meal did not. Thus, the sensitivity of post-feeding natriuresis is between 50 and 100 mmols Na. As post feeding natriuresis is a naturally occurring physiological event it should provide a useful paradigm for the investigation of mechanisms controlling Na balance.

Effects of sodium intake on lactation and Na levels in body fluids of Blackface ewes.

1. A low-sodium diet was given to Blackface ewes over two reproductive seasons; the diet provided 3-7 mmol Na daily, except for the period of lactation, when Na intake was increased to around 11 mmol/d. The diet of the control ewes was supplemented with sodium chloride to provide the recommended allowance of about ten times the level in the experimental low-Na diet. 2. Milk production was assessed during the first 2 months of lactation from incremental changes in the live weight of lambs during controlled sucking periods. Na and potassium were determined in milk and also in plasma, saliva and urine. 3. Neither yield nor concentration of Na and K in milk was affected by the level of Na in the diet. These results were supported by the similarity in live-weight gain of lambs in both years regardless of diet. 4. Plasma Na and K concentrations were not affected by the level of dietary Na. Na concentration in saliva and urine was significantly lower in the treated than in the control ewes, and K concentration in saliva was significantly higher.

Role of atrial natriuretic peptide in adaptation of sodium excretion with reduced renal mass.

The kidney maintains constancy of body fluid volume by regulating urinary sodium (Na) excretion. In chronic renal failure, the reduction in glomerular filtration rate (GFR) is accompanied by an increase in Na excretion per nephron if dietary Na intake is not changed. Reduction in Na intake in proportion to reduced GFR obviates this adaptive increase in tubule Na excretion. To examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the enhanced Na excretion per nephron in chronic renal failure, we studied rats subjected to 5/6 nephrectomy or sham operation on low, normal, and high Na intakes. Urinary Na excretion increased with increasing dietary Na in all groups, and Na excretion per nephron was increased in 5/6 nephrectomized rats as compared with sham-operated rats on the higher Na intakes. Plasma ANP levels were unaffected by dietary Na manipulations in sham-operated rats, but rose progressively in 5/6 nephrectomized rats with increasing Na intake. Despite extensive nephron reduction, however, plasma ANP levels failed to rise in uremic rats on low Na diets and in this group Na excretion per nephron also failed to rise. We conclude that enhanced ANP secretion may play an important role in promoting the adaptive increase in Na excretion per nephron in chronic renal failure. Restriction of dietary Na in the setting of reduced GFR obviates the stimulation of ANP secretion as well as the adaptive increase in Na excretion rate per nephron.

Phosphoinositide Turnover in Erythrocyte Membranes in Human and Experimental Hypertension

The metabolism of phosphoinositides, a class of membrane lipids involved in Ca2+ -transport and/or mobilization systems was investigated in patients with moderate essential hypertension and in Sabra rats. Experiments were performed in vitro on isolated erythrocyte membranes by measuring the 32P-labelling of phosphatidylinositol 4,5-bisphosphate (PI-P2) and of phosphatidylinositol 4-phosphate (PI-P) following the incubation of membranes with [gamma-32P] ATP. In untreated essential hypertensives (n = 31) or in hypertensive patients whose blood pressure was controlled by beta-blocker therapy (n = 20), 32P-PI-P2 was significantly higher than in normotensive controls (n = 30); no significant difference was observed between the two groups of hypertensive patients. In Sabra rats fed on a low Na diet, 32P-PI-P2 levels were significantly higher in hypertensive-prone animals (SBH) than in hypertensive-resistant animals (SBN). When the animals were fed a high Na diet or were DOCA/salt treated, 32P-PI-P2 did not change in either substrain, although such conditions differentially affected the blood pressure of SBH and SBN. Our data indicate that the modification of phosphoinositide metabolism is not a consequence of the blood pressure elevation, but can be considered as an intrinsic membrane defect which may be associated with functional alterations of Ca2+ fluxes which in hypertensives result in an enhanced intracellular Ca2+ level.

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHR) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given 'low' (LNa), 'control' and 'high' (HNa) Na diets (0.5, 5 and 50 mmol X 100 g-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P less than 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P less than 0.01) and in WKY 489 versus 393 bpm (P less than 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and 'intrinsic' pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.

Effect of spironolactone on fluid volumes and adrenal steroids in primary aldosteronism.

Plasma volume (PV) and extracellular fluid volume (ECF) were determined in 7 patients with essential hypertension (controls) and in 10 patients with primary aldosteronism, while on a high Na diet (342 mEq/day) and on a low Na diet (12 mEq/day). The volume studies were repeated in 6 of the primary aldosteronism patients during treatment with spironolactone for over 3 months. Plasma renin activity (PRA), plasma aldosterone concentration (PAC), cortisol concentration, and serum Na and K concentrations were measured in all patients while on a Na-restricted diet (85 mEq/day) as well as on high-Na and low-Na diets. There were no significant changes in arterial pressure during different Na diets in any groups of patients with essential hypertension, or primary aldosteronism with and without spironolactone therapy. Spironolactone treatment normalized the arterial pressure in patients with primary aldosteronism at all Na intakes. These patients had greater values for PV and ECF than did those with essential hypertension. Spironolactone treatment reduced PV during the low-Na diet, but did not alter it during the high-Na diet. Spironolactone did not produce significant changes in ECF during either the high-Na or low-Na diets. Although there were no changes in PV and ECF in patients with primary aldosteronism due to changes in Na intake, both PV and ECF were significantly less in these patients during spironolactone treatment and in patients with essential hypertension during low-Na intake than during high-Na intake. With primary aldosteronism, PRA was depressed and PAC was elevated when compared to essential hypertension, these were not altered by different Na diets in the patients with primary aldosteronism as they were in those with essential hypertension. During treatment with spironolactone the PRA was restored to normal and showed normal changes with variations in dietary Na, but PAC remained elevated during spironolactone. Plasma cortisol was the same among those with essential hypertension and patients with untreated and spironolactone-treated primary aldosteronism. Serum K was less in untreated primary aldosteronism during all Na diets than in essential hypertension, but during spironolactone it was restored to normal. These results suggest that in primary aldosteronism the reduction in arterial pressure by spironolactone treatment does not occur simply by reductions in body fluid volumes. The long-term treatment of patients with primary aldosteronism with spironolactone does not inhibit the production of aldosterone, possibly because of enhanced activity of the renin-angiotensin system and an increase in serum K.

Prostaglandin in renin release during sodium deprivation.

This study was designed to examine the role of prostaglandins in the macula densa-mediated increase in plasma renin activity (PRA) during dietary sodium deprivation in rats. Micropuncture collections of early distal (ED) tubular fluid (TF) and measurements of PRA, arterial pressure (AP), and renal blood flow (RBF) were obtained in four groups of animals. Groups I and II received a normal Na diet and groups II and IV received a low Na diet; groups II and IV received indomethacin. Studies were performed after surgical denervation of the kidneys; AP and RBF were not different among the four groups of animals. EDTFna delivery was lower in groups III (0.20 +/- 0.04 neq/min) and in group IV (0.16 +/- 0.01 neq/min) animals on the low Na diet as compared with group I (0.34 +/- 0.02 neq/min) and group II (0.32 +/- 0.05 neq/min) animals on the normal Na diet. In association with the lower EDTFna delivery, the animals receiving vehicle in group III had an elevated PRA (31.46 +/- 8.81 ng/ml) as compared with group I animals on the normal Na diet receiving vehicle (4.78 +/- 1.64 ng/ml). This rise in PRA was abolished in the animals in group IV (4.06 +/- 0.81 ng/ml) that received indomethacin. We conclude that the increase in PRA, possibly resulting from macula densa receptor stimulation, during dietary Na deprivation is dependent on prostaglandin synthesis.

Water and sodium excretion in unilaterally denervated normal and sodium depleted anesthetized rats before and after plasma volume repletion

The possible role of a reduction in plasma volume (PV) by surgery as well as the importance of dietary Na supply in denervation natriuresis have been investigated on Inactin-anesthetized male rats subjected to acute unilateral renal sympathectomy. Four groups were studied: I. Normal Na diet (n = 14); II. Low Na diet (boiled rice for 2 weeks) -- isotonic glucose infusion (n = 10); III. Low Na diet -- isotonic saline infusion (n = 5); IV. Normal and low Na diet rats served as conscious control (n = 10). Surgery caused a 9-11% increase in hematocrit and a 15-18% decrease in PV in groups I-III. Plasma volume repletion (PVR) reverted these changes. In group I sodium excretion from both kidneys was only a fraction of that in conscious animals kept on the same diet (group IV) and marked denervation natriuresis was observed. After PVR sodium output of innervated (I) kidneys was not different from that of conscious rats but denervated (D) kidneys excreted twice that amount. In group II Na excretion was increased compared to conscious Na depleted controls, and PVR augmented further this difference. Surprisingly, the difference in urinary sodium excretion (UNaV) between I and D kidneys was absent after surgery and was minimal after PVR in this group. In group III physiological saline infusion reverted the effect of Na depletion and denervation natriuresis was present both before and after PVR. It is concluded that PV reduction does not play a major role in denervation phenomenon. In Na depleted anesthetized rats denervation natriuresis is absent or minimal.

Diurnal and longitudinal variations in human milk sodium and potassium: implication for nutrition and physiology

Human milk sodium ([Nal]) and potassium ([K)] concentrations were measured every 4 h for 24 h in 28 subjects 3.5 to 32 wk postpartum. A diurnal variation in milk Na was seen, which was reciprocal to K. Significant negative correlations between Na and K were seen in these periods: 3.5 to 6; 8 to 18, 20 to 32 wk postpartum (p less than 0.01 for each). The mean 24 h milk sodium concentrations (x(Na)) decreased between 3.5 and 18 wk postpartum (p less than 0.005 by paired t test). Changes in mean potassium (-XK) were not statistically significant. Diet apparently does not affect milk Na. Administration of a low Na diet: 10.8 +/- .9 (SD) mEq Na/day and 60 to 100 mEq K/day for 2 days did not change x(Na). But urinary Na decreased 7-fold as aldosterone increased 5-fold. No significant correlation was seen between 24 h Na excretion in urine and x(Na) in milk (n = 51). A significant positive correlation was seen between urinary K and -XK in milk (r = 0.36), p less than 0.001).

Dietary chloride modifies renin release in normal humans.

The effect of high and low chloride diets on the responses of plasma renin activity (PRA), angiotensin II (ANG II), and aldosterone (Aldo) to upright posture was studied in the same normal subjects in balance on constant sodium intake. Diet 1 consisted of 10 meq Na/day (low Na) and either 50 or 150 meq Cl/day. Diet 2 consisted of 200 meq Na/day (high Na) and either 20 or 200 meq Cl/day. The mean recumbent PRA level on the high Na-high Cl diet tended to be lower than on the high Na-low Cl diet but was not significantly different. However, the absolute peak upright PRA levels, 8.8 +/- 1.0 vs. 4.4 +/- 0.8 ng . ml-1 . h-1, and the incremental difference (delta PRA) between recumbent and peak upright PRA levels, 5.5 +/- 0.8 vs. 2.2 +/- 0.5 ng . ml-1 . h-1, were significantly less on the high Na-high Cl diet compared with the high Na-low Cl diet. Similar significant changes were seen in ANG II and Aldo levels. However, there were no significant changes in PRA, ANG II, and Aldo responses to upright posture on the low Na diet when the dietary Cl was varied. It is concluded that dietary Cl is another factor modifying renin release. However, Cl is probably less important than Na because Cl-induced changes in PRA were not seen in the low salt state.

163 ROLE OF THE RENIN-ALDOSTERONE SYSTEM IN HYPERTENSION COARCTATION OF THE AORTA

The role of the renin-aldosterone system in the etiology of hypertension due to coarctation of the aorta was evaluated in pre-operative adolescents hospitalized in the Pediatric Clinical Research Center. Five patients aged 12-20 years were studied. Blood pressure was 146/82 to 170/115 in 4 patients and 130/84 mm Hg in a 12 year old. Variable sodium (Na) diets were administered during hospitalization. Patients received normal Na (100-150 meq/day), low Na (10 meq/day), and high Na (250 meq/day) diets for a minimum of 3 days/diet. Potassium (K) intake was maintained at 50 meq/day. Daily 24-hour urinary aldosterone (aldo), Na, and K excretions were obtained. Plasma renin activity (PRA) was measured at rest and after ambulation. Patients received no medication. All were in K balance and had normal serum K. The aldo response to changes in dietary Na was qualitatively and quantitatively normal when compared to the nomogram of New et al. The response of PRA to differential Na diets was also qualitatively normal. However, PRA was more variable than previously reported in adults. In some patients, the response of PRA to ambulation and/or low Na diet was higher than reported adult standards. The significance of this response requires further evaluation. We conclude that the renin-aldosterone system was intact in these hypertensive adolescents with coarctation of the aorta.

Mineralocorticoid response to low dose adrenocorticotropin infusion.

The adrenocorticoid responses to low dose ACTH of plasma aldosterone (aldo), corticosterone (B), 11-deoxycorticosterone (DOC), 18-hydroxycorticosterone (18-OHB), 18-hydroxycorticosterone (18-OH-DOC), and cortisol (F) were compared. Alpha ACTH-)1-24) was infused beginning at 0800 h at increasing rates from 12.5-200 mIU/30 min in supine normal subjects under the following conditions: 1) regular Na (120 meq) diet, 2) low Na (10 meq) diet, 3) dexamethasone preadministration (0.5 mg every 6 h for 48 h), and 4) night study (2000 h; 120 meq Na intake). Plasma 18-OH-DOC and B demonstrated quantitatively the greatest responses to ACTH, while DOC and 18-OHB responses were intermediate. Increments in aldo and F were least after ACTH and were maximum at 50 mIU/30 min ACTH, whereas other corticosteroids demonstrated linear responses up to infusion rates of 200 mIU/30 min. All corticosteroids, however, were similar in their threshold responses to ACTH which were at infusion rates of approximately 7-9 mIU/30 min. Na restriction enhanced aldo and 18-OHB responses to ACTH 2- to 3-fold but did not alter the other corticosteroid responses. Dexamethasone pretreatment augmented aldo, 18-OHB, and F responses but did not change the responsitivity of the other corticosteroids to ACTH. Adrenal corticosteroid responses to ACTH were not significantly different between 0800 and 2000 h in subjects on 120-meq Na intake. Thus, corticosteroids show markedly different responses to physiological doses of ACTH, which may have more importance in their regulation than heretofore proposed. Dexamethasone pretreatment enhances aldo, 18-OHB, and F responses to ACTH but does not affect the responses of other corticosteroids. Contrary to reports in experimental animals, corticosteroid responses to ACTH in man do not differ from day to night.

BLOOD PRESSURE AND HORMONAL CHANGES FOLLOWING ALTERATION IN DIETARY SODIUM AND POTASSIUM IN YOUNG MEN WITH AND WITHOUT A FAMILIAL PREDISPOSITION TO HYPERTENSION

The blood pressures (BP) of the parents of a group of students were determined and two subgroups of students were defined, one with (PHT group) and one without (PNT group) a familial predisposition to hypertension. Observations were made in both groups during three periods of modified dietary electrolyte intake: (i) no-added sodium (low Na), (ii) no added sodium with potassium supplementation (low Na/high K), and (iii) sodium supplementation (high Na). The diets were given in random order. At the start of the trial, while the students continued their customary diet, the PHT group had higher systolic and diastolic pressures and plasma noradrenaline levels than the PNT group. At the end of 4 weeks of the high Na diet, the BP levels of both groups were significantly higher than those after the low Na diet. In contrast, when the low Na diet was supplemented for 2 weeks with potassium, BPs of the PHT group fell significantly, while those of the PNT group rose slightly. BP in the PHT group was significantly lower during the low Na/high K than during the high Na diet (systolic 10·5 mm Hg±2·3 SE; diastolic 11·2±2·5, the changes being significantly different from those in the PNT group. The changes in plasma renin and aldosterone were similar in both groups during the different diets. Plasma noradrenaline fell in the PHT group, but rose in the PNT group when the low Na diet was supplemented with potassium. This fall in plasma noradrenaline in the PHT group during the low Na/high K diet correlated with the falls in systolic and diastolic BP. It is concluded that whereas young adults with a familial predisposition to hypertension behave similarly to those without such a predisposition in having a pressor response to a high sodium intake, they are peculiar in showing a depressor response to a high potassium intake.

THE ROLE OF RENAL PROSTAGLANDIN E AND KALLIKREIN IN PATHOGENESIS OF ESSENTIAL HYPERTENSION

The present study was done to investigate the interrelationships between renal kallikrein-kinin, renal prostaglandin E and renin-angiotensin-aldosterone systems in human and the possibility that renal kallikrein-kinin and renal prostaglandin E may participate in the pathogenesis of essential hypertension by means of measuring urinary excretion of kallikrein and prostaglandin E, plasma renin activity and plasma aldosterone concentration before and after stimulation or inhibition of the renin-angiotensin-aldosterone system and inhibition of renal prostaglandin E generation. Urinary kallikrein excretion was increased after the stimulation of the renin-angiotensin-aldosterone system by low Na diet or the administration of furosemide and upright posture, while it tended to decrease after the inhibition of the renin-angiotensin-aldosterone system by the administration of 1-sarcosine-8-isoleucine angiotensin II under sodium depletion or spironolactone. These data showed that the changes in urinary kallikrein excretion paralelled with those of the renin-angiotensin-aldosterone system following various stimuli, suggesting that renal kallikrein-kinin system may regulate blood pressure by opposing the action of the renin-angiotensin-aldosterone system. Urinary PGE excretion was decreased after sodium depletion and increased after the administration of furosemide in spite of the augmentation of the renin-angiotensin-aldosterone system. The changes in urinary PGE excretion was closely related to those in urinary Na output after various stimuli and a significant positive correlation was found between basal levels of urinary PGE and those of urinary Na, suggesting that renal prostaglandin E may be involved in the regulation of blood pressure by affecting renal sodium handing. The present data showed that basal level of urinary excretion of PGE and kallikrein was lower in essential hypertension than in normal subjects and that the release of renal kallikrein and PGE after furosemide administration was also suppressed in essential hypertension compared with that in normal subjects, suggesting that there exists an impaired defense mechanism against the renin-angiotensin-aldosterone system resulting in sodium retention.

Aldosterone effects on electrolyte transport of the lower intestine (coprodeum and colon) of the fowl ( Gallus domesticus) in vitro

Hens were maintained on commercial (high-Na) poultry food or on a wheat and barley (WB; low-Na) diet. Stripped mucosae from coprodeum and colon were mounted in a Ussing chamber, and short-circuit current ( I sc), electrical potential difference (PD), and tissue resistance were measured. Tissue responses to addition of amino acids and amiloride were assessed. Coprodeum from commercial-diet birds had near-zero I sc and PD. WB diet enhanced the average I sc to 201 μA/cm 2 and the PD to 33 mV. The I sc and PD were abolished by amiloride, but were not responsive to amino acids. Colon from commericial-diet birds had fairly high I sc (134 μA/cm 2) and PD (10 mV); I sc and PD were increased by amino acids (by 45%) and not affected byamiloride. WB diet augmented I sc to 379 μA/cm 2 and PD to 20 mV, abolished amino acid sensitivity, and induced almost complete sensitivity to amiloride. Birds maintained on WB diet had higher plasma aldosterone concentrations (9.6 pg/100 μl) than commercial-diet birds (5.8 pg/100 μl), but diet did not affect plasma corticosterone concentrations. In vivo injections of aldosterone (32–128 μg/kg body weight) into commercial-diet birds induced changes in I sc and PD of coprodeum and colon, and changes in amino acid and amiloride sensitivity of colon, resembling the changes associated with WB maintenance, but of generally lesser magnitude. It is concluded that aldosterone injections reproduced qualitatively all the effects of a low-Na diet.

Prevention with thiazide of NaCl-induced hypertension in Dahl "S" rats. Evidence for a Na-retaining humoral agent in "S" rats.

Dahl S rats become hypertensive wben fed > high salt (NaCl) diet but remain normotensive on a low NaCl diet. Dahl R rats are normotensive on either diet. For a given perfusion pressure, isolated S kidneys excrete 50% less sodium than R kidneys. Therefore, we searched for a sodium-retaining hormone in S rats. Kidneys were isolated without ischemia from rats and were continuously perfused at 125 mm Hg with blood from Dahl S and R rats, all on low NaCl diets. All kidney and adrenal tissue had been extirpated from the perfusing rats. During 15 minutes of perfusion, the isolated normal kidneys excreted a mean of 164 jtEq Na/rain/100 g during 26 perfusion experiments with blood from R rats. The normal kidneys excreted a mean of 84 j*Eq Na during 24 perfusions with blood from S rats. Thus, the kidneys excreted half as much sodium wben perfused with S blood compared with R blood (p < 0.02). Seemingly, a Na-retainlng humoral agent is present in the blood of S rats on a low Na diet, in the absence of renal and adrenal tissue. Moreover, in these kidneys, perfusion with S blood induced a 16% higher renal vascular resistance than perfusion with R blood (p < 0.01), indicating vasoconstricting agents in S blood. However, the Na-retaining humoral effect is definitely not dependent on the vasoconstriction. The Na-retaining humoral effect in S blood could lead to Na retention by S kidneys in vivo, which could partially account for the susceptibility of S rats to NaCl hypertension. Furthermore, both S and R perfusing rats were continuously expanded with two-thirds blood and one-third Ringer's solution at a rate of 5% of body weight per hour. This expansion induced the appearance of a natriuretic humoral agent in the blood of both S and R rats to an equal degree, so that after 45 minutes of expansion, the isolated kidneys had increased their Na excretion approximately twofold. Hypertension is readily induced in Dahl S rats by feeding them a high NaCl diet. However, this hypertension can be almost completely prevented by concomitant treatment with thiazide diuretics that act mainly on the kidney to facilitate sodium excretion. This result is in agreement with the hypothesis that a shift in the pressure nttriuresis curve, reducing Na excretion for a given arterial pressure, is partially responsible for the great sensitivity to NaCl hypertension in the S rat. The Naretaining hormone may contribute to this shift.(Hypertension 1: 316-323, 1979)

Sodium transport in the hen lower intestine. induction of sodium sites in the brush border by a low sodium diet.

1. The fluxes of Na were measured on isolated coprodeal mucosa at 1--220 mM-Na from hens on low (L) and high (H) Na diets with the purpose of finding the location and characteristics of Na sites activated in the cellular pathway by L. 2. The influx across the brush border, JNamc, and the transmural fluxes, JNasm and JNams, were determined. Effects on these fluxes of ouabain, 10(-3) M in the serosal solution, and amiloride, 10(-4) M in the mucosal solution, were studied for both dietary states. 3. JNamc was 5--22 (L) and 0--0.8 (H) muequiv/cm2.hr at 130 mM-Na corrected for the paracellular flux of Na. The JNamc (H) is tenfold smaller than found by Choshniak, Munck & Skadhauge (1977). This discrepancy is at present inexplicable. Amiloride completely inhibited JNamc (L). Preincubation in 0 or 130 mM-Na had no effect on JNamc. Ouabain reduced JNamc (L) by only about 37% after preincubation at 130 mM-Na. The Kt of JNamc was 5.1 (L) and 50.6 (H) mM-Na. 4. JNasm was 50 (H) and 61 (L) n-equiv/cm2.hr at 6.5 mM-Na. Ouabain increased JNasm by 360% in the low Na state. The increased JNasm was inhibited 74--100% by amiloride. This is interpreted as a ouabain induced Na-Na exchange at the basolateral Na-K-ATPase and an almost complete block of JNacm by amiloride. A similar exchange of Na at the basolateral membrane in the high-Na state was revealed by 'opening' the brush border for Na with monensin added to the mucosal solution. Amiloride in itself prevented a 50% recirculation of Na via the paracellular route and back across the cells in the low Na state. 5. JNams was 5.6 (L) muequiv/cm2.hr and 187 (L) microA/cm2 at 6.5 mM-Na. Amiloride reduced these values to 0.4 muequiv/cm2.hr and 5.8 microA/cm2. On addition of amiloride the transmural resistance in (L) coprodea at 130 mM-Na increased from 140 to 190 and it remained unchanged at 260 omega cm2 in (H) coprodea. The resistance of (L) birds, 163, was not affected by ouabain, 166 (L) omega cm2. 6. 20:1 NaCl dilution potentials at the mucosal side of 17--18 mV (L) and nearly zero (H) had half-times around 1 sec. Amiloride eliminated completely these diffusion potentials. The short half-time indicates a location in the brush border of sodium specific sites induced by the low-Na diet. This conclusion is oppsite to that described by Choshniak et al. (1977). 7. Ion selectivity, voltage--current and conductance--concentration relations in the presence of amiloride indicated a weakly cation selective and highly hydrated pathway, which was also thick and with neutral sites. This fits a paracellular route with the limiting barrier for ions at the tight junction.