Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene "knockout" mice.

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulation of salt balance by reducing tubular reabsorption of sodium and chloride. Therefore, in the chronic absence of this hormone, a defect of salt excretion should be evident. We used an ANP gene deletion model to test this premise. F2 homozygous mutant mice (-/-) and their wild-type littermates (+/+) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. Arterial blood pressures, renal excretions of salt and water, as well as collecting duct transport of fluid and electrolytes were measured. Pressures were significantly higher in -/- compared with +/+ mice (139 +/- 4 vs. 101 +/- 2 mmHg; 1 mmHg = 133.3 Pa). There was no difference in glomerular filtration rate (-/- = 0.84 +/- 0.06; +/+ = 0.81 +/- 0.04 mL x min(-1) x g(-1) kidney weight). In the collecting duct, sodium and chloride reabsorptions were significantly higher in the -/- group than in the +/+ group. As a result, natriuresis and chloruresis were relatively reduced (U(Na)V: -/- = 8.6 +/- 1.1; +/+ = 14.0 +/- 1.1; U(Cl)V: -/- = 10.1 +/- 1.4; +/+ = 16.0 +/- 1.1 micromol x min(-1) x g(-1) kidney weight). We conclude that the absence of endogenous ANP activity in mice on a high-salt diet subjected to acute saline infusion causes inappropriately high reabsorption of sodium and chloride in the medullary collecting duct, resulting in a relative defect in renal excretory capacity for salt.

Body fluid volume status and the renal response to atrial natriuretic peptide in rats.

The effect of altering the volumes of different body fluid compartments on the renal response to atrial natriuretic peptide (ANP) was studied in anesthetized rats before and during administration of the peptide at 170 ng/min. Four different groups were used. In the first (De), reduction of total body water content was induced by 48 h water deprivation. In the second (De+NaCl), an acute intravenous infusion after the same 48 h dehydration was used to restore the extracellular, but not the intracellular, fluid compartment. In the third (Eu+NaCl), euvolemic rats were infused with isotonic saline at the same rate as in group De+NaCl to expand both intravascular and interstitial components of extracellular fluid. In the fourth group (Eu+BSA) an infusion of hyperoncotic (6%) bovine serum albumin in isotonic saline was used to expand the intravascular volume while contracting the interstitial volume. Excretion of water and salt was predictably reduced in the De group compared with the others. This reduction was associated with increased tubular reabsorption, both upstream from the medullary collecting duct and in the duct itself. Administration of ANP did not significantly affect diuresis and saluresis, or tubular transport. By contrast, there were marked and similar diuretic and natriuretic responses to ANP in groups De+NaCl and Eu+NaCl, associated with transport inhibition primarily in the medullary collecting duct. Surprisingly, the rats infused with hyperoncotic solution (Eu+NaCl) also failed to show marked excretory or duct transport responses to ANP. According to the study design, the two nonresponding groups had, respectively, a decreased or a normal intracellular compartment, and a decreased or increased plasma volume. The common feature of both nonresponding groups was a decreased interstitial fluid compartment, whereas the two responding groups had normal or increased interstitial volume. We suggest, therefore, that a replete interstitial fluid compartment is essential for the renal response to ANP.

Effect of sympathetic and angiotensin-aldosterone systems on renal salt conservation in the rat.

During dietary salt deprivation, the sympathetic nervous system and the angiotensin-aldosterone system are stimulated. Both systems are thought to be essential for maximal salt conservation by the kidney. To study their relative contributions, we produced negative salt balance in rats by intraperitoneal injection of furosemide, followed by a low-salt diet (<0.008% NaCl). In a 1-wk metabolic study, the animals were unable to replace the drug-induced salt deficit. Six groups of rats were studied. A control group established baseline function, a second group of 6-hydroxydopamine (OHDA) rats were treated with OHDA to destroy sympathetic efferent nerve terminals, and a third group (losartan) were treated with the angiotensin-receptor antagonist losartan. The influence of catecholamines and aldosterone released from the adrenal gland was studied in a further three groups. Rats were sham-adrenalectomized (sham), subjected to bilateral adrenal enucleation (Enuc) to eliminate catecholamine secretion, or were bilaterally adrenalectomized (Adx), eliminating both catecholamine and corticosteroid release. Dexamethasone was used as glucocorticoid replacement in this group. Steady-state urinary salt excretion was not different between control and OHDA rats. The losartan group showed significantly increased sodium but not chloride excretion. Surprisingly, there were no differences in salt excretion among sham, Enuc, and Adx groups. We conclude that, during a state of chronic salt depletion, renal mechanism(s) independent of neuronally released or systemically circulating catecholamines or of adrenally released aldosterone can ensure maximal salt conservation by the kidney. Although our data show that losartan increased sodium excretion under these conditions, we suggest that the losartan effect can be explained by a reduction of bicarbonate reabsorption, obligating simultaneous excretion of the cation.

Renal resistance to ANF in salt-depleted rats is independent of sympathetic or ANG-aldosterone systems.

Chronic salt depletion was used as a model to study the mechanism of renal resistance to the natriuretic effect of atrial natriuretic factor (ANF). Rats were pretreated with furosemide and placed on a low-salt diet (<0.008% NaCl) for 1 wk before a clearance experiment. Compared with animals on a normal salt diet (0.4% NaCl), the natriuretic reponse to ANF administration was reduced by one order of magnitude and was quantitatively trivial. To assess the influence of the sympathoadrenergic system, different groups of rats were either subjected to acute unilateral renal denervation, to chronic adrenal enucleation to reduce circulating catecholamines, or to pretreatment with 6-hydroxydopamine (OHDA) to destroy sympathetic postganglionic nerve endings. None of these treatments was able to fully or even partially restore ANF natriuresis. To determine whether an effect of angiotensin on the kidney prevented the response, the specific receptor antagonist losartan (DuP-753) was administered during the week prior to the experiment. This treatment also did not influence ANF resistance. Similarly, bilateral adrenalectomy 2 wk before the experiment did not affect the renal ANF resistance in salt-depleted rats. The depressed excretory response could not be explained on the basis of reduced renal perfusion pressure or glomerular filtration rate. We conclude that undetermined compensatory mechanism(s) ensures renal salt conservation in this model in the face of even supraphysiological levels of ANF.

Blood pressure and fluid-electrolyte balance in mice with reduced or absent ANP.

Atrial natriuretic peptide (ANP)-gene knockout mice of three genotypes (+/+, +/-, and -/-) were maintained on a low-salt diet (0.008% NaCl). They were then fed either the same low-salt diet or a high-salt diet (8% NaCl) for 1 wk. No differences were found among genotypes in daily food and water intakes or in urinary volume and electrolyte excretions. Arterial blood pressures measured in anesthetized animals at the end of the dietary regimen were significantly and similarly increased in -/- compared with +/+ mice on each diet. Renal excretion of fluid and electrolytes was measured in anesthetized mice before and after acute blood volume expansion. No genotype differences were observed before volume expansion. After volume expansion the wild-type (+/+) mice had much greater saluretic responses than either the heterozygous (+/-) or the homozygous mutant (-/-) animals on the low-salt diet but not on the high-salt diet. We conclude that ANP lowers blood pressure in the absence of detected changes in renal function; ANP is not essential for normal salt balance, even on high-salt intake; and ANP is essential for the natriuretic response to acute blood volume expansion on a low-salt but not high-salt intake.

Effect of bradykinin B2 receptor antagonist and indomethacin on natriuretic and hypotensive responses to atrial natriuretic factor.

The effects of inhibition of bradykinin and prostaglandin on the renal and blood pressure responses to atrial natriuretic factor (ANF) were studied in anesthetized rats. Intraarterial infusion of the receptor antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin (BKA) at 14 micrograms/min, a rate sufficient to block the hypotensive response to 250 micrograms of bradykinin, did not affect the natriuresis due to injection of ANF (UNaV: control, before ANF, 393 +/- 101, after ANF, 2322 +/- 400 nmol/min; BKA, before ANF, 261 +/- 72, after ANF, 2259 +/- 390 nmol/min). In contrast, infusion of indomethacin (Indo) reduced the level of sodium excretion both before and especially after ANF administration (UNaV: Indo, before ANF, 75 +/- 15, after ANF, 320 nmol/min). The effect of combining BKA with Indo was not different from the effect of Indo alone (UNaV: BKA + Indo, before ANF, 119 +/- 26, after ANF, 469 +/- 167 nmol/min). The bradykinin antagonist, with or without Indo, was associated with significant hypotension relative to control. Indo, both in the absence and presence of the antagonist, was associated with a progressive decrease in blood pressure compared with control. However, in each the hypotensive responses to ANF were not different from those in the control group. We conclude that under the present experimental conditions bradykinin does not modify ANF-induced natriuresis. However, inhibition of prostaglandin synthesis by Indo is associated with renal salt retention, reducing natriuresis both before and after ANF administration.

Dietary salt extremes and renal function in rats: effect of atrial natriuretic factor.

1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (< 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment. 2. Baseline sodium chloride excretion was 6480 +/- 810 nmol min-1 g-1 kidney weight in group 1 compared to 99 +/- 16 in group 1. Fractional reabsorptions in the medullary collecting duct were 37 +/- 6% and 95 +/- 2% of delivered load, respectively (P < 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 +/- 1.0% of filtered load in group 1 and 2.7 +/- 0.7% in group II (P < 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Proximal tubular function in transgenic mice overexpressing atrial natriuretic factor.

A transgenic mouse model in which atrial natriuretic factor (ANF) expression is targeted to the liver was used to study intrarenal adjustments to the chronically elevated hormone level. Such animals, designated TTR-ANF, are characterized by reduced arterial blood pressure but similar sodium excretion compared with nontransgenic siblings. Proximal tubular micropuncture gave the following results: single-nephron filtration rate = 12.7 +/- 1.1 vs. 15.6 +/- 1.9 nL/min (TTR-ANF versus nontransgenic, ns); end-proximal tubular fluid/plasma concentration ratio of inulin = 1.93 +/- 0.09 vs. 1.97 +/- 0.15 (ns); fractional reabsorption of sodium = 45.5 +/- 2.8 vs. 46.0 +/- 3.8% (ns); fractional reabsorption of chloride = 33.6 +/- 3.3 vs. 32.4 +/- 4.1% (ns). These data indicate that life-long elevation of plasma ANF concentration was not associated with significant alteration in single-nephron filtration rate and proximal tubular function. We conclude that compensatory antinatriuretic mechanisms, localized downstream from the proximal tubule, can prevent ANF natriuresis.

Lack of biologic activity or specific binding of amino-terminal pro-ANP segments in the rat.

In addition to atrial natriuretic peptide (ANP99-126) itself, linear peptide fragments from its N-terminal prohormone segment (pro-ANP) have been reported to have biological activity. In vivo, diuresis and natriuresis, as well as hypotension have been observed. In vitro, sodium uptake into medullary collecting duct cells was inhibited, and tone of vascular smooth muscle was reduced, associated with activation of guanylate cyclase. Such previous studies have used heterologous peptides and species, e.g., human pro-ANP1-30 or pro-ANP31-67, tested in rat, pig, or dog. The present experiments were designed to test whether rat pro-ANP1-30 or pro-ANP31-67 were natriuretic and hypotensive in rats, whether the two peptides showed specific binding to plasma membranes from rat kidney cortex or aorta, and whether they affected particulate guanylate cyclase activity in rat glomerular membranes. To extend in vitro results from the literature, the effect of human pro-ANP31-67 on transport in the rat medullary collecting duct in vivo was also tested. Although rat ANP99-126, as expected, increased diuresis and natriuresis, associated with inhibition of transport in the medullary collecting duct, in identically treated rats human pro-ANP31-67 was without effect. Similarly, only the ANP99-126 infusion resulted in reduction of arterial blood pressure. Furthermore, no diuretic, natriuretic, or hypotensive responses were observed in rats infused with either rat pro-ANP31-67 or pro-ANP1-30. In plasma membranes from rat kidney cortex or aorta, neither of the rat prosegments showed specific binding, or interference with ANP99-126 receptors. Finally, in contrast to ANP99-126, neither of the prosegments was able to increase basal guanylate cyclase activity in rat glomerular membranes. Therefore, under our experimental conditions we were unable to replicate the earlier results. This study thus does not support a regulatory role for pro-ANP fragments in blood volume or blood pressure homeostasis.

Cardiovascular and renal functional effects of an antagonist of the guanylyl cyclase-linked ANF receptor.

A selective antagonist for the cGMP-linked ANF receptor was used to assess inhibition of cardiovascular and renal actions of atrial natriuretic factor (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle, respectively, prior to an infusion of ANF. A third group received neither antagonist injection nor ANF infusion and served as a time control. Compared to ANF infusion alone, prior antagonist administration was associated with significant reduction of both the hypotension and hemoconcentration following peptide infusion, although significant residual effects were still present. Glomerular filtration rates during ANF infusion were significantly lower in the antagonist group. The increases in urinary salt and water excretion were also partially blocked by the antagonist. Microcatheterization studies showed significant partial reversal of ANF-induced inhibition of sodium chloride and water reabsorption in the medullary collecting duct. We conclude that the antagonist is an effective specific blocker of the cardiovascular, renal hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate the regulatory roles of this peptide hormone system.

The effect of isoproterenol on fluid and electrolyte transport in the inner medullary collecting duct.

In the late distal and cortical collecting tubule, which is the principal regulatory site for potassium (K) excretion, vasopressin stimulates, and epinephrine via beta-adrenergic action, inhibits K secretion. In the inner medullary collecting duct (IMCD) we have shown that vasopressin also stimulates K secretion. The present experiments were designed to determine whether the beta-adrenergic agonist, isoproterenol, would induce K reabsorption in the IMCD, and (or) prevent a secretory response to acute KCl infusion. Two groups of rats, with or without isoproterenol administration (3 micrograms/h), were subjected to retrograde microcatheterization of the IMCD before and during infusion of 0.83 mol/h KCl. Isoproterenol reduced plasma K concentration and urinary K excretion, but the response to acute KCl infusion was qualitatively similar to control. Isoproterenol decreased delivery of potassium, chloride, and fluid to the IMCD, there was no net transport of K along the duct in either group, and KCl infusion did not result in K secretion in either group. The results indicate that isoproterenol may inhibit K secretion in the late distal or cortical collecting tubule. However, there was no statistically significant difference in K transport along the IMCD between isoproterenol and control groups. Reduced sodium excretion, which was found during isoproterenol administration both before and after KCl infusion, was associated with no change in sodium delivery but with increased sodium reabsorption in the IMCD. This increased sodium reabsorption may be a direct effect of isoproterenol, or may be due to reflex cardiovascular adjustments associated with systemic actions of the drug.

Nephron site responsible for the reduced kaliuretic response to mineralocorticoids during hypokalemia in rats.

Rats with hypokalemia induced by eating a low-K diet have a diminished kaliuretic response to mineralocorticoids. The purpose of this study was to determine if this was the due to a lower rate of net secretion of K in the cortical collecting duct (CCD) and/or an enhanced rate of reabsorption of K in the medullary collecting duct (MCD). Secondary active secretion of K in the CCD raises the [K] in the lumen as compared to the plasma [TF/P)K). If the (TF/P)K is greater than 1, there was secondary active secretion of K in this nephron segment. The (TF/P)K in the CCD was measured by microcatheterization of the collecting duct. Three groups of rats were studied: rats on a low-K diet with and without the acute administration of DOCA, and rats on a normal-K diet treated with DOCA on a chronic basis. Rats on the low-K diet had a (TF/P)K of 0.8 +/- 0.11; this value did not rise to values significantly greater than 1 after the acute administration of DOCA (1.4 +/- 0.35). In contrast, chronic administration of DOCA to rats fed a normal-K diet did result in a (TF/P)K which was significantly greater than unity (3.1 +/- 0.39). The degree of hypokalemia was not significantly different in these rats. The absolute and fractional reabsorption of K in the MCD was not different in the rats on the low-K diet with or without DOCA. We conclude that the nephron segment which is responsible for the reduced kaliuretic response to mineralocorticoids is the CCD.

Endogenous natriuretic peptides: effect on collecting duct function in rat kidney.

In vivo microcatheterization of the medullary collecting duct of rat kidney was used to compare the functional effects of intravenous infusion of rat atrial natriuretic factor, human urodilatin (a peptide produced in the kidney), or porcine brain natriuretic peptide. All three peptides resulted in striking and quantitatively similar inhibition of NaCl and water reabsorption in the duct. In addition, all three induced significant K+ secretion in this part of the nephron. These results could not be explained by functional alterations in upstream tubular segments. We conclude that the three peptides are equivalent in their transport effects on the inner medullary collecting duct system, when administered at the same (presumably supramaximal) dose.

In vivo microperfusion of inner medullary collecting duct in rats: effect of amiloride and ANF.

A method is described that allows perfusion of the inner medullary collecting duct (IMCD) of the rat kidney in situ and in vivo. Fine polyethylene catheters connected to a microperfusion pump were inserted into collecting ducts via the openings at the exposed papilla tip. Perfusate contained 22Na as well as [3H]inulin. During perfusion at 30 nl/min, urine was simultaneously collected. A decrease in the Na-to-inulin concentration ratio in the urinary sample, compared with the perfusate, was taken as indicating unidirectional efflux of Na from the perfused duct system. The effects of luminal amiloride (2 X 10(-4) M) or atrial natriuretic factor (ANF, 10(-8) M) were studied. Compared with control perfusions, both agonists reduced Na efflux from the IMCD to approximately 50%, indicating luminal sites of action. Combination of amiloride and ANF at their respective concentrations had no further effect. The lack of statistically significant additivity suggests, but does not prove, that ANF, administered from the luminal side, is able to block amiloride-sensitive Na channels in the apical membrane of IMCD cells.

Effects of increased perfusion pressure on medullary collecting duct function.

The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 +/- 4.1 to 51 +/- 9.3% (p less than 0.01) and from 65.7 +/- 6.0 to 42.7 +/- 9.1% (p less than 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.

Effects of chronic hypokalaemia and adrenalectomy on potassium transport by the medullary collecting duct of the rat.

1. The purpose of this study was to evaluate the roles of chronic hypokalaemia and of aldosterone in K+ transport in the medullary collecting duct. Renal clearance and duct transport measurements were made before and after KCl infusion in three groups of animals: normal rats on a regular K+ diet (group I), and sham-operated (II) or adrenalectomized rats (group III), both on a low K+ diet. 2. Only the sham-operated animals on the low K+ diet became hypokalaemic. They also had the lowest rate of K+ excretion at the time of study. Adrenalectomized rats were normokalaemic, and had an intermediate rate of K+ excretion. After the acute KCl infusion, kaliuresis remained significantly depressed in the rats which were previously hypokalaemic. In contrast, K+ excretion rates in response to K+ infusion were high and not significantly different in both previously normokalaemic groups, independent of the presence of the adrenal glands. 3. In the medullary collecting duct, before the KCl infusion there was no net K+ transport in either normokalaemic group (I and III). However, after the KCl infusion there was significant K+ secretion in both of these groups (32% and 22% of total urinary excretion, respectively). In contrast, the sham-operated hypokalaemic rats on the low K+ diet had a small absolute, but large fractional K+ reabsorption (64% of delivered load) in the medullary collecting duct. With KCl infusion in this group, K+ delivery to the medullary duct increased, but absolute reabsorption along the duct was maintained, resulting in a fractional reabsorption of 28% of delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

Inner medullary collecting duct function in ischemic acute renal failure.

Inner medullary collecting duct function in ischemic acute renal failure: The purpose of this study was to determine the role of the medullary collecting duct in the increased urine sodium concentration, decreased urine osmolality, and altered potassium excretion with hyperkalemia which are characteristic of ischemic acute renal failure. Microcatheterization of the inner medullary collecting duct (0.1 to 5 mm from papillary tip) was carried out in rats 24 h after bilateral renal artery clamping for 45 min (n = 8) or sham-operated (n = 8). In ischemic acute renal failure (ARF), tubular fluid osmolality did not increase significantly along the inner medullary collecting duct (IMCD). Tubular fluid sodium concentration was similar to controls at the beginning of the IMCD but was significantly higher at the papillary tip. Tubular fluid to plasma potassium concentration ratio (TF/PK) increased to a greater extent along the IMCD in ischemic ARF than in controls. During acute KCl loading in two additional groups, tubular fluid potassium concentration and TF/PK were much lower at the beginning of the IMCD in ischemic ARF than in controls but increased similarly along the IMCD. In ischemic ARF, with or without KCl loading, renal tissue electrolytes showed reduced potassium concentration in the outer medullary region. The results indicate that impaired IMCD function contributes significantly to the increase in urine sodium concentration and the decrease in urine osmolality which are characteristic of ischemic acute renal failure. In ischemic ARF with mild hyperkalemia, an adaptive increase in K secretion occurred in the IMCD. Severe hyperkalemia and decreased potassium excretion during acute potassium loading in ischemic ARF were determined in more proximal nephron segments and were associated with decreased outer medullary tissue potassium, presumably due to tubular necrosis. Decreased outer medullary tissue potassium could contribute to hyperkalemia by diminishing K secretion in the pars rectae and descending limbs or in the cortical and outer medullary collecting ducts.

Interaction of amiloride and hydrochlorothiazide with atrial natriuretic factor in the medullary collecting duct.

Medullary collecting duct function was studied using the in vivo microcatheterization technique in three groups of rats receiving amiloride, hydrochlorothiazide, or both diuretics. In each group of animals, atrial natriuretic factor (ANF99-126) was given in the second phase of the experiment. The combination of amiloride and hydrochlorothiazide resulted in a more marked natriuresis than either diuretic given as a single agent. Sodium reabsorption in the medullary collecting duct, as a fraction of the delivered load, was reduced from 64% (amiloride) and 69% (hydrochlorothiazide) to 29% (amiloride and hydrochlorothiazide). Atrial natriuretic factor reduced collecting duct sodium reabsorption when added to amiloride or hydrochlorothiazide to 23% and to 41%, respectively, but had no additional effect when given with amiloride and hydrochlorothiazide. Potassium excretion with amiloride and hydrochlorothiazide was intermediate between amiloride or hydrochlorothiazide given as single agents. With the diuretic combination, potassium transport showed no significant reabsorption or secretion along the medullary collecting duct, amiloride was associated with potassium reabsorption, and hydrochlorothiazide was associated with potassium secretion in the duct. The results confirm the importance of the medullary collecting duct as a site of diuretic action. The known additive effects of amiloride and hydrochlorothiazide on sodium excretion and the opposing effects of these agents on potassium excretion occur, to a major degree, in the medullary collecting duct. Furthermore, the additive effects of amiloride and ANF indicate that blocking of amiloride-sensitive sodium channels is not the only mechanism of action of ANF on duct salt transport in vivo.

Renal responses to saline and atrial natriuretic factor infusions in Dahl rats.

Weanling Dahl rats of the salt-sensitive and salt-resistant strains were kept either on a low salt diet for 10-15 weeks, or the diet was supplemented with 7% NaCl for the last 30 days. Animals were anesthetized and the renal responses to acute saline infusion and infusion of synthetic atrial natriuretic factor (ANF) were studied on both dietary regimens. Arterial blood pressures of sensitive and resistant groups were not different on the low salt intake. As expected, addition of dietary salt increased pressure markedly in the sensitive animals. Resistant rats also had smaller, but statistically significant, increases in pressure. On the low salt diet, salt-sensitive rats showed a larger renal response to saline infusion, whereas on the high salt diet there were no significant differences between strains. The responses to ANF infusion were not different between groups on either diet, although NaCl feeding potentiated the natriuresis and diuresis. Under the conditions of the present experiments there was, therefore, no indication that Dahl salt-sensitive rats had a relative inability to respond either to an acute saline load or to exogenous ANF administration.

Effect of vasopressin analogue (dDAVP) on potassium transport in medullary collecting duct.

The microcatheterization technique was used to examine electrolyte transport in the medullary collecting duct of two groups of anesthetized rats during water diuresis and during a second experimental phase with 1-desamino-8-D-arginine vasopressin (dDAVP) administration or continued water diuresis. Potassium reabsorption of 53-61% of the delivered load was consistently observed in the medullary collecting duct during water diuresis. During dDAVP administration, urinary potassium excretion doubled, and there was no net potassium transport (reabsorption or secretion) in the medullary collecting duct. The change in potassium transport in medullary collecting duct from water diuresis to antidiuresis (dDAVP) was sufficient to account for the increase in urinary potassium excretion. Changes in flow rate, luminal sodium concentration, or collecting duct sodium reabsorption could not account for the changes in potassium transport in the collecting duct during dDAVP. The results are interpreted as indicating that dDAVP stimulates potassium entry (secretion) into the medullary collecting duct, probably by a direct effect. This action of antidiuretic hormone appears to be important in maintaining potassium homeostasis during changing water balance.