Efflux Of Na Research Articles

Potentiation by Bay-K-8644 of the adrenal catecholamine secretory response to Ca re-introduction: Possible activation of Ca influx linked with Na efflux: Masaru Sorimachi, Kazuhiko Yamagami and Shigeto Nishimura, Department of Physiology, Kagoshima University School of Medicine, Kagoshima 890, Japan

Potentiation by Bay-K-8644 of the adrenal catecholamine secretory response to Ca re-introduction: Possible activation of Ca influx linked with Na efflux: Masaru Sorimachi, Kazuhiko Yamagami and Shigeto Nishimura, Department of Physiology, Kagoshima University School of Medicine, Kagoshima 890, Japan

Thiol-dependent K:Cl transport in sheep red cells: VIII. Activation through metabolically and chemically reversible oxidation by diamide.

The sulfhydryl (SH) oxidant diamide activated in a concentration-dependent manner ouabain-resistant (OR), Cl-dependent K flux in both low potassium (LK) and high potassium (HK) sheep red cells as determined from the rate of zero-trans K efflux into media with Cl or Cl replaced by NO3 or methane sulfonate (CH3SO3). Diamide did not alter the OR Na efflux into choline Cl. The diamide effect on K efflux appeared after 80% of cellular glutathione (GSH) was oxidized to GSSG, its disulfide. The stimulation of K efflux was completely reversed during metabolic restitution of GSH, a process that depended on the length of exposure to and the concentration of diamide. The action of diamide on both the K:Cl transporter and GSH was also fully reversed by the reducing agent dithiothreitol (DTT). Diamide apparently oxidized the same SH groups alkylated by N-ethylmaleimide (NEM) (Lauf, P.K. 1983. J. Membrane Biol. 73:237-246). Like NEM, diamide activated K:Cl transport several-fold more in LK cells than in HK cells, and the effect on LK cells was partially inhibited by anti-L1, the allo-antibody known to inhibit OR K fluxes.

Effects of internal Na and external K concentrations on Na/K coupling of Na,K-pump in frog skeletal muscle.

To clarify the dependency of the Na/K coupling of the Na,K-pump on internal Na and external K concentrations in skeletal muscle, the ouabain-induced change in membrane potential, the ouabain-induced change in Na efflux and the membrane resistance were measured at various internal Na and external K concentrations in bullfrog sartorius muscle. Upon raising the internal Na concentration from 6 mmol/kg muscle water to 20 mmol/kg muscle water, the magnitude of the ouabain-induced change in membrane potential increased about eightfold and the magnitude of the ouabain-induced change in Na efflux increased about fivefold while the membrane resistance was not significantly changed. As the external K concentration increased from 1 to 10 mM, the magnitude of the ouabain-induced change in membrane potential decreased (1/5.5 fold), while the magnitude of the ouabain-induced change in Na efflux increased (about 1.5-fold). The membrane resistance decreased upon raising the external K concentration from 1 to 10 mM (1/2-fold). These observations imply that the values of the Na/K coupling of the Na,K-pump increases upon raising the internal Na concentration and decreases upon raising the external K concentration.

Erythrocyte sodium transport in Bartter's syndrome.

Erythrocyte sodium transport was evaluated by measurement of intracellular Na concentration (ICNa), 22Na efflux rate constant (NaERC) and 3H-ouabain binding (BMax) (reflecting the number of Na/K ATPase pump sites) in 9 children with Bartter's syndrome compared to controls (children and adults) and children with various forms of salt wasting disease. There were no differences between control children and adults. In untreated Bartter's syndrome ICNa was significantly increased with NaERC and BMax significantly decreased compared to findings in controls and patients with other salt wasting disease. On prostaglandin synthetase inhibitor (Indomethacin) therapy, ICNa decreased but remained higher than in controls, NaERC increased to normal values but BMax remained low. These data support the view that there is a widespread defect in membrane electrolyte transport in Bartter's syndrome but suggest that the benefit of indomethacin therapy is not manifest via an effect on Na/K ATPase.

Na+-K+-ATPase-dependent sodium flux in cortical collecting tubule.

The instantaneous rate of efflux of intracellular Na was studied in rabbit isolated cortical collecting tubules (CCT) as a function of temperature and intracellular Na concentration ([Na]i). [Na]i of microdissected CCT was increased by cold and K-free exposure in the presence of 22Na and the extracellular tracer [3H] sorbitol. [Na]i rose rapidly to 40 mM at 30 min, after which it rose more slowly, reaching 120-140 mM at 6 h. Kinetics of Na efflux were studied after rapid rewarming, using a special device allowing measurements at 20-s intervals. Under control conditions, the total Na load was extruded in less than 8 min, whereas, in the presence of 10(-4) M ouabain, only 50% of the load was extruded during this period of time. Ouabain-sensitive Na efflux was first evident at 13 degrees C and gradually increased between 13 and 35 degrees C. At 37 degrees C, Na+-K+-ATPase-dependent Na efflux was dependent on [Na]i. This efflux gradually increased, from 0.05 to 0.5 peq.nl tubular volume-1.s-1 as a function of [Na]i and reached a plateau at 70 mM [Na]i. It is concluded that [Na]i is a major modulator of the pump activity in CCT; at normal levels of [Na]i, the pump is operating at only a small fraction of its total capacity.

Effects of pH, potential, chloride and furosemide on passive Na+ and K+ effluxes from human red blood cells.

Ouabain-resistant effluxes from pretreated cells containing K+/Na+ = 1.5 into K+ and Na+ free media were measured. Furosemide-sensitive cation effluxes from cells with nearly normal membrane potential and pH were lower in NO3- media than in Cl- media; they were reduced when pH was lowered in Cl- media. When the membrane potential was positive inside furosemide increased the effluxes of Na+ and K+ (7 experiments). With inside-positive membrane potential the furosemide-insensitive effluxes were markedly increased, they decreased with decreasing pH at constant internal Cl- and also when internal Cl- was reduced at constant pH. The correlation between cation flux and the membrane potential was different for cells with high or low internal chloride concentrations. The data with chloride greater than or equal to 47 mM showed a better fit with the single-barrier model than with the infinite number-of-barriers model. With low chloride no significant correlation between flux and membrane potential was found. The data are not compatible with pure independent diffusion of Na+ and K+ in the presence of ouabain and furosemide.

Altered chloride transport in arteries from aldosterone salt-hypertensive rats

Chronic infusion of d-aldosterone into uninephrectomized rats on high sodium intake resulted in a significant increase in systolic blood pressure. The steady state efflux of 36Cl in aorta and femoral artery of hypertensive rats was significantly elevated compared to that in arteries of control rats. These elevations in chloride efflux persisted in the presence of the Cl-HCO3 exchange inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), and in Cl-HCO3 free solution. The Cl-HCO3-dependent component of the 36Cl efflux was also higher under some conditions. DIDS (100 mumol/l), also significantly reduced the increase in 36Cl efflux caused by norepinephrine (NE) in one of four groups, but had no significant effect on the NE stimulated 42K efflux. Contractile responses to both NE and KCl were unaffected by DIDS treatment. Therefore, it appears that Ca influx and release mechanisms function normally in the presence of DIDS. Similarly, DIDS had either a small or no effect on 42K movements under basal conditions. A slight reduction in the passive efflux of 24Na was observed in aortic smooth muscle exposed to DIDS with no significant effect on active Na transport. These findings indicate that DIDS is reasonably selective for Cl exchange sites in vascular smooth muscle during an exposure of 15 min or less and has little effect on cationic transport processes. The application of this blocker as well as anion substitution indicates that an elevation in the 36Cl leak efflux and related Cl permeability of arterial smooth muscle is associated with aldosterone-salt hypertension.

The effect of Intralipid infusion on the human leucocyte sodium-pump in vivo.

1. The effect of unsaturated long-chain non-esterified fatty acids (NEFA) on the human leucocyte sodium-pump was studied in vivo. 2. Plasma NEFA level was raised acutely from 0.28 (SD 0.10) to 2.54 (SD 0.48) mmol/l by infusion of 'Intralipid 20%' (trademark) at 90 ml/h with heparin, and the human leucocyte 22Na efflux rate constants were studied in eight normal weight males. 3. After 3 h, there was a significant lowering of the total (from 3.97 (SD 0.92) to 3.10 (SD 0.71)/h; P less than 0.01) and ouabain-sensitive 22Na efflux rate constants (from 2.89 (SD 0.55) to 2.37 (SD 0.62)/h; P less than 0.02). Ouabain-insensitive efflux rate constants showed a tendency to fall (from 1.08 (SD 0.51) to 0.73 (SD 0.23)/h). Leucocyte potassium content remained unchanged, but sodium content rose from 31 (SD 12) to 38 (SD 18) mmol/kg dry weight (P less than 0.05). Total, ouabain-insensitive and ouabain-sensitive efflux rates did not change significantly during the Intralipid-heparin infusion. 4. Plasma insulin levels rose gradually throughout the 3 h infusion period. 5. In conclusion, NEFA, when raised to pathological levels, can inhibit the leucocyte Na-pump in vivo even in the presence of physiological levels of serum albumin, and may increase insulin secretion.

Two functionally distinct forms of guanosine cyclic 3',5'-phosphate stimulated cation channels in a bovine rod photoreceptor disk preparation

Cyclic nucleotide stimulated efflux of 22Na+ and 45Ca2+ from a purified bovine rod outer segment disk preparation was measured on the 25-100-ms time scale by a novel rapid superfusion method. Activation of cation efflux by 8-bromoguanosine cyclic 3',5'-phosphate (8-Br-cGMP) was maximal within 25 ms. Over a wide range of concentrations of 8-Br-cGMP, the kinetics of termination of efflux precisely conformed to the sum of two exponential decay processes: a rapid phase (decay constant of 200 ms) and a slower phase (decay constant of 1.6 s). The kinetics of the biphasic decay of efflux cannot be explained by depletion of a pool of releasable 22Na but appear to reflect an intrinsic process for inactivation of the channels. 8-Br-cGMP-stimulated release of actively accumulated 45Ca exhibited identical biphasic decay kinetics. The maximum rate of Ca release [5 nmol.(mg of disk protein)-1.min-1] may be sufficient to produce a 1 microM change in local cytoplasmic [Ca] within 20 ms. The Ca:Na selectivity ratio is approximately 0.5:1 for both decay phases. 8-Br-cGMP demonstrated a lower potency (EC50 of 8.4 microM vs 2.8 microM) but a higher degree of cooperativity in its activation of the rapid vs the slower decay phase of 22Na efflux. The slower phase of decay was selectively inhibited by 25 microM l-cis-diltiazem, a relatively weak inhibitor of the rapid decay phase. Sodium ion (5-10 mM) selectively inhibited the rapid decay phase of 8-Br-cGMP-stimulated 45Ca release. These two kinetically and pharmacologically distinct phases of decay are hypothesized to represent two functionally distinct forms of cGMP-stimulated cation channels.

New quinoxalinediones show potent antagonism of quisqualate responses in cultured mouse cortical neurons

Two new quinoxalines, DNQX (6,7-dinitro-quinoxaline-2,3-dion = FG 9041) and CNQX (6-nitro-7-cyano-quinoxaline-2,3-dion = FG 9065), were tested as antagonists of excitatory amino acid responses in cultured neurons and brain slices. DNQX and CNQX showed potent competitive antagonism of quisqualate and kainate induced [ 3H]GABA release from cultured mouse cortical neurons with weaker effects on NMDA responses (Schild values for DNQX were 6.2, 5.9 and 5.4, respectively). Also in a model of excitatory amino acid induced 22Na efflux from striatal slices DNQX blocked responses to quisqualate and kainate more effectively than responses to NMDA.

Sodium-lithium exchange in sarcolemmal vesicles from canine superior mesenteric artery.

Exchange of intracellular sodium for extracellular lithium readily occurs in vascular smooth muscle, but the mechanism of this exchange is not known. These studies examined whether a sodium-lithium countertransport system was present in the cell membrane of vascular smooth muscle. A sarcolemmal-enriched vesicle preparation was obtained from canine superior mesenteric artery via a magnesium aggregation and differential centrifugation technique. An outwardly directed gradient for lithium stimulated 22Na uptake by the vesicles, and an inwardly directed gradient for lithium stimulated 22Na efflux. These effects were not due to an alteration in membrane potential, and sodium uptake was not stimulated by lithium in the absence of a gradient for lithium. The lithium gradient-stimulated component of sodium uptake was not affected by a change in membrane potential and was insensitive to ouabain. Both sodium-lithium exchange and sodium-proton exchange in sarcolemmal-enriched vesicles were inhibited by two compounds that inhibit the sodium-lithium countertransport system in red cells, phloretin and quinidine. Ethylisopropylamiloride also inhibited both sodium-lithium exchange and sodium-proton exchange in the vesicles. In support of the possibility that sarcolemmal sodium-lithium exchange and sodium-proton exchange are mediated by a single cation exchange mechanism with affinity for sodium, lithium, and protons, we found that an inwardly directed sodium or lithium gradient stimulated proton efflux, and that the stimulation of sodium efflux by external lithium or protons was not additive. It is concluded from these studies that sarcolemmal vesicles from canine superior mesenteric artery contain an electroneutral, phloretin, quinidine, and ethylisopropylamiloride inhibitable sodium-lithium exchange transport system.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymmetry of Na-K-Cl cotransport in human erythrocytes.

The Na-K-Cl cotransport system in human erythrocytes was studied by measuring net influxes and effluxes of Na and K. The influx of K was shown to be stimulated by Na and the influx of Na was stimulated by K, satisfying the fundamental criterion of cotransport. In addition, these mutually stimulating cation influxes had a stoichiometry of 1:1 and were entirely inhibited by furosemide; these results are also consistent with cotransport. Furthermore, the mutually stimulating influxes were entirely dependent on Cl, since they were abolished when nitrate was substituted for Cl. In contrast, cotransport, defined by mutual dependence of fluxes, was not detected in the outward direction over a range of cellular Na and K concentrations from 0 to 50 mmol/l cells. The cotransport pathway did, however, appear to mediate a Na-stimulated K efflux (but no K-stimulated Na efflux), and furosemide-inhibitable effluxes of both Na and K. Nitrate (but not sulfate) appeared to substitute for chloride in promoting Na-stimulated K efflux. Thus the Na-K-Cl cotransport system in human red cells is intrinsically asymmetric, and mediates coupled cation fluxes readily only in the inward direction.

The human leucocyte sodium pump in Cushing's syndrome.

Because corticosteroids have important effects on sodium homeostasis, we studied leucocyte 22Na efflux in patients with Cushing's syndrome. The ouabain-sensitive 22Na+ efflux rate constant was raised in Cushing's syndrome (mean +/- SD 2.84 +/- 0.32 vs 2.35 +/- 0.53/h, P less than 0.001, n = 15). This efflux rate constant correlated with the urinary free cortisol (rs = 0.61, P less than 0.02), but less significantly with the 0900 h plasma cortisol (rs = 0.46, P less than 0.08). There was no correlation with the supine plasma aldosterone. Intracellular sodium content was significantly lower in Cushing's syndrome (21.1 +/- 4.6 vs 27.8 +/- 9.5 mmol/kg dry weight, P less than 0.01), with a raised intracellular potassium to sodium content ratio (16.1 +/- 3.3 vs 12.9 +/- 3.6, P less than 0.01). After treatment of the Cushing's syndrome by trans-sphenoidal adenomectomy or adrenalectomy, these defects in cellular sodium balance were corrected. Thus, the distribution of sodium between intra- and extracellular fluid may be affected by adrenal corticosteroids via an action on the sodium pump.

Interaction between aldosterone and vasopressin on vascular smooth muscle permeability to sodium

The s.c. injection of aldosterone (10 μg/kg) induces a release of vasopressin. The peak of plasma vasopressin level occurs at the same time as the late in vivo effect of aldosterone on passive 22Na efflux from arterial smooth muscle. These results indicate that vasopressin mediates the delayed in vivo effects of aldosterone on ouabain-insensitive 22Na efflux, since on the other hand, it has been possible to show that the action of the peptide is accelerated by a previous exposure to the mineralocorticoid. Indeed, after a 120-min pretreatment with 10 −8 M aldosterone, vasopressin induces an effect on 22Na efflux in 30 min, as opposed to the 120 min needed in the absence of the steroid.

Bioenergetic properties of alkalophilic Bacillus sp. strain C-59 on an alkaline medium containing K2CO3.

Alkalophilic Bacillus sp. strain C-59 could grow well on an alkaline medium containing K2CO3, as well as Na2CO3, but did not grow on K+-depleted medium. Right-side-out membrane vesicles, energized in the absence of Na+, however, could not take up [14C]methylamine actively, while vesicles equilibrated with 10 mM NaCl actively took up [14C]methylamine. The uptake of [14C]serine was also stimulated by the addition of Na+, and the imposition of a sodium gradient caused transient uptake. These results indicated that an Na+/H+ antiporter was involved in pH homeostasis and generation of an electrochemical sodium gradient in strain C-59 even though a growth requirement for Na+ was not evident. The efflux of 22Na+ from 22Na+-loaded vesicles was more rapid at pH 9.5 than at pH 7 in the presence of an electron donor. On the other hand, vesicles at pH 7 showed more rapid efflux than at pH 9.5 when the antiporter was energized by a valinomycin-mediated K+ diffusion potential (inside negative).

Effect of short term triiodothyronine administration on human leukocyte Rb(K) influx and Na efflux.

The effect of short term T3 administration on leukocyte ouabain-sensitive 86Rb(K) influx and Na efflux in normal subjects was investigated. At a dose of 60 micrograms daily for 7 days, T3 induced a significant increase in leukocyte 86Rb(K) influx and a significant fall in plasma K concentrations. Plasma and intracellular Na concentrations did not change. [3H]Ouabain binding, a measure of Na-K ATPase units, did not change. A week after T3 administration, 86Rb(K) influx, Na efflux, and plasma K concentrations were normal. In a series of five hyperthyroid patients, both ouabain-sensitive 86Rb influx and [3H]ouabain binding were significantly greater than in normal subjects. We conclude that T3 stimulates 86Rb(K) influx and Na efflux by leukocytes in vivo independently of [3H]ouabain binding and that this increase is rapidly reversible. However, in hyperthyroid patients both 86Rb influx and [3H]ouabain binding are increased, probably due to prolonged exposure to thyroid hormone excess.

An investigation of sodium‐calcium exchange in the smooth muscle of guinea‐pig ureter.

1. After application of ouabain (10(-4) M), the intracellular Na+ activity (alpha iNa) of smooth muscle cells in the guinea-pig ureter stabilizes at a relatively low level which can be rapidly lowered by reduction of external Na+ (Na+o) or elevation of Ca2+o. Both these procedures also elicit a transient contracture. These observations have previously been interpreted as evidence for Na+-Ca2+ exchange. The presence of such an exchange mechanism has now been further investigated by measurements of alpha iNa, tension, ion analysis and 22Na efflux. 2. Ion analysis demonstrated that tissues were able to maintain a high cellular K+ content in the presence of ouabain, but slowly lost K+ and gained Na+ if K+o was also removed, as expected for an infinite outward gradient for K+ and a fully inhibited Na+ pump. 3. Tissues were only able to maintain a low cellular Na+ and high cellular K+ in the presence of ouabain if Ca2+ was present in the bathing solution. Reduction of Ca2+o to very low levels also caused a continual slow rise in alpha iNa in the presence of ouabain, provided that the prolonged depolarization caused by these low levels was prevented by elevation of Mg2+o. Alteration of the membrane potential by changing K+o at constant Na+o showed that alpha iNa decreased by about 1.2 mM for a 10 mV depolarization, within the range from -70 to -30 mV. 4. A small Ca2+o-activated 22Na efflux was observed in ouabain-treated tissues in the absence of Na+o. 40 mM-Ca2+ was not more effective at activating this efflux than was 2.5 mM-Ca2+, while 40 mM-Mg2+ was ineffective. Restoration of the normal Na+o caused a large increase in the rate of 22Na loss. 5. Application of Mn2+ in the presence of ouabain caused a slow rise in alpha iNa and a small decline in resting tension. The fall in alpha iNa on reduction of Na+o was slowed by the presence of Mn2+ (mean half-time increased from 1.7 to 5.0 min) and the concomitant contracture was almost abolished. These results are consistent with a Mn2+-induced inhibition of Na+-Ca2+ exchange. However, the fall in alpha iNa induced by elevation of Ca2+o was unaffected by the presence of Mn2+ and the attendant contracture was, if anything, enhanced. 6. Observation of changes in alpha iNa and tension at various Mn2+ and Ca2+ concentrations demonstrated a competitive interaction between the two divalent cations.(ABSTRACT TRUNCATED AT 400 WORDS)

THE EFFECT OF ORAL GLUCOSE ON THE LEUCOCYTE SODIUM PUMP IN NORMAL AND OBESE SUBJECTS

The effect of oral glucose (40 g/m2 body surface area) on the leucocyte 22Na efflux rate constants (ERC) was studied in 13 normal weight and 10 obese subjects. The ouabain-sensitive 22Na ERC was higher in leucocytes isolated from fasting obese subjects (median [range] for obese 2.77 [2.33-3.11] vs normals 1.91 [1.57-2.77] h-1, P less than 0.001). There was no difference in the ouabain-resistant 22Na ERC. Oral glucose raised the ouabain-sensitive 22Na ERC after 2 h in normal subjects (1.91 [1.57-2.77] to 2.41 [2.11-3.02] h-1, P less than 0.001). The ouabain-resistant 22Na ERC fell from 0.71 [0.32-1.10] to 0.46 [0.35-0.68] h-1, P less than 0.008. Conversely, in obese subjects, the ouabain-sensitive ERC fell (2.77 [2.33-3.11] to 2.59 [2.11-2.92] h-1, P less than 0.06). There was no significant change in ouabain-resistant 22Na ERC 2 h after oral glucose. The fasting leucocyte 22Na ouabain-sensitive ERC correlated with fasting plasma insulin levels and insulin resistance (rs = 0.48, P less than 0.01 for both). The change in this ERC with oral glucose correlated with the incremental insulin response over 2 h (rs = -0.53, P less than 0.006) and to the insulin resistance (rs = -0.56, P less than 0.003). The failure of oral glucose to stimulate the leucocyte sodium pump in obesity could partially account for the defect in dietary thermogenesis in obesity. This defect in stimulation of the sodium pump is related to insulin resistance.

Na/Ca exchange in barnacle muscle cells has a stoichiometry of 3 Na+/1 Ca2+.

The portions of the 45Ca influx and 22Na efflux that were activated by physiological concentrations of intracellular free Ca2+, [Ca2+]i, were studied in internally perfused single giant barnacle muscle cells. Since both fluxes were activated by intracellular Ca2+ (Cai) and the Ca influx was dependent on internal Na+ (Nai), the fluxes appear to be coupled (Na/Ca exchange). Tracer Ca/Ca and Na/Na exchanges were eliminated by employing tris(hydroxymethyl)aminomethane (Tris) as the predominant external cation. Under these circumstances, the ratio of the external Ca2+ (Cao)-dependent, Cai-activated Na+ efflux to the Nai-dependent, Cai-activated Ca influx was 3.1-3.2 Na+/1 Ca2+, when the intracellular Na+ concentration, [Na+]i was either 30 or 46 mM. This is the first direct measurement of the Na/Ca exchange stoichiometry. In many types of cells, the Na/Ca exchange system appears to operate in parallel with a plasma membrane ATP-driven Ca pump that has a lower capacity (maximum velocity), but higher affinity for Ca2+ than the Na/Ca exchanger. The data on the stoichiometry and activation by internal Ca2+ imply that the turnover of the Na/Ca exchanger is modulated during periods of cell activity. When the cells are depolarized, the Na/Ca exchange system is activated by the rising [Ca2+]i, and Ca2+ entry via the exchanger is promoted. Then, at repolarization, Ca2+ exits rapidly, primarily via the exchanger. However, in resting cells, with a low [Ca2+]i, much (but not all) of the Ca2+ efflux is probably mediated by the ATP-driven Ca pump.

DECREASED ERYTHROCYTE Na+ PUMP ACTIVITY IN NORMOTENSIVE CHILDREN OF HYPERTENSIVE PARENTS

Increased erythrocyte (RBC) intracellular Na+ and depressed RBC Na+-pump activity (NaPA) occur in adults with essential hypertension (EH). Lithium-Na countertransport (Na influx) has been found to be increased in RBC of normotensive (N) children of hypertensive parents, and may serve as a marker for later EH. To examine whether RBC NaPA (Na efflux) was also associated with parental EH, and perhaps with an increased likelihood of subsequent EH, we assayed ouabain-sensitive 86Rb-uptake in the RBC of 61 N children, 41 with N parents (Group I), and 20 with at least 1 parent with EH (Group II). RBC NaPA was assessed both in plasma from the same subject and in a Krebs buffer. when NaPA was assayed in plasma, values were significantly lower in Group II, 3.07 ± 0.39 (mean ± sem) nmol/mg prot/30 min, compared to Group I, 4.35 ± 0.36 (p W), but no statistical significance. Thus, in a small biracial sample, NaPA was inhibited in N children whose parent(s) had EH. This may prove to be a sensitive marker for adult-onset EH, allowing prospective detection, intervention, and possible prevention of EH.