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Biomedical subjects

J B Field

Publications and source records attributed to J B Field.

At least 37 records · Page 2Linked to original sources
PubMed1989

Hypoglycemia. Definition, clinical presentations, classification, and laboratory tests.

Hypoglycemia can be defined as the occurrence of a wide variety of symptoms in association with a plasma glucose concentration of 50 mg per dl or less. It may be asymptomatic, and the relief of the symptoms by administration of glucose is not sufficient to establish a diagnosis. Although the symptoms may be quite variable, they can be classified as adrenergic or neuroglycopenic. Hypothermia, hyperthermia, or localizing neurologic findings may be seen as a consequence of hypoglycemia. Severe, repeated episodes of hypoglycemia can cause a distal neuropathy that is primarily motor but can also have a sensory component. Hypoglycemia can be classified as fasting, reactive, surreptitious, or artifactual. Some causes of hypoglycemia are unique to infants and children. Underlying diseases such as liver disease, endocrine disease, or renal disease can be diagnosed by the characteristic physical findings and laboratory tests. Other causes of hypoglycemia can be identified by a variety of diagnostic tests involving measurement of glucose, insulin, C-peptide, and other related compounds.

Blood Glucose↗
PubMed1988

Hepatic extraction of somatostatin in conscious dogs.

Fractional hepatic extraction of endogenous somatostatin immunoreactivity was examined in conscious dogs with Doppler flow probes on the portal vein and hepatic artery and catheters in the portal and hepatic veins and carotid artery before and after induction of hypoglycemia by infusion of insulin. Insulin infusion (1 and 2 mU.kg-1.min-1) decreased arterial plasma glucose from 76 +/- 4 mg/dl to a nadir of 41 +/- 2 mg/dl. Basal portal vein somatostatin was 117 +/- 11 pg/ml, which was significantly greater than the 97 +/- 12 pg/ml in the hepatic vein (P less than 0.05) and 79 +/- 8 pg/ml in the carotid artery (P less than 0.05). Hypoglycemia significantly augmented portal vein somatostatin to 206 +/- 32 pg/ml with parallel increases in the hepatic vein and carotid artery. The mean basal fractional hepatic extraction of total somatostatin immunoreactivity was 9 +/- 6% and was unchanged during hypoglycemia (14 +/- 4%). Column chromatography of the portal vein somatostatin immunoreactivity in the basal period yielded three peaks with most of the material eluting with somatostatin-14 and the void volume. Very little somatostatin-28 was detected. There was very little hepatic extraction of the void volume material while approximately 50% of somatostatin-14 was removed by that organ. After insulin-induced hypoglycemia, there was the greatest percent increase in somatostatin-28 and a doubling of somatostatin-14 and the void volume material. Most of the somatostatins-14 and -28 were removed by the liver, while extraction of the void volume material was negligible.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Acidosis-induced glucose intolerance is not prevented by adrenergic blockade.

The determinants of the altered glucoregulation in acidosis were investigated in anesthetized dogs. Because CO2 rapidly equilibrates and its effects are mediated by pH changes, CO2 inhalation was examined. Plasma acid-base composition, glucose, insulin, glucagon, and blood flows were evaluated before and after an intravenous glucose load (1.2 +/- 0.1 g/kg body wt) in normal and acidotic dogs with flow probes and catheters chronically implanted in the portal circulation. A simultaneous infusion of phentolamine (5 micrograms.kg-1.min-1), propranolol (3.5 micrograms.kg-1.min-1), both, or none was used. All acidemic dogs had lower hepatic extraction of insulin and greater hyperglycemia after the glucose challenge; thus the adrenergic system is not critical for these responses. Because arterial insulin levels were either normal (propranolol) or increased (all others) in acidosis, insulin resistance was likely. Insulin infusion (2 and 4 mU.kg-1.min-1) with euglycemic clamp and [3-3H]glucose documented that acidemia decreases peripheral glucose utilization and the insulin suppression of hepatic glucose production. Acidemia also enhances plasma glucagon levels, yet this effect plays a limited role in the observed hyperglycemia.

Acid-Base Equilibrium↗
PubMed1988

Comparison of effects of thyrotropin, phorbol esters, norepinephrine, and carbachol on iodide organification in dog thyroid slices, follicles, and cultured cells.

The effect of TSH, phorbol ester, norepinephrine (NE), and carbachol, agents known to influence thyroid metabolism, was compared on iodide organification in dog thyroid slices, freshly isolated follicles, and cultured cells. TSH stimulated iodide organification in all three types of preparations, and this effect was mimicked by (Bu)2cAMP. In contrast, the phorbol ester, tetradecanoyl phorbol acetate (TPA) stimulated iodide organification in slices and follicles but inhibited it in cells. The dose and time required for these divergent effects were similar. Other stimulators of protein kinase C such as aplysiatoxin and teleocidin mimicked the effects of TPA, and these effects were partially reversed by H-7, an inhibitor of protein kinase C. Pretreatment of cells with TPA for 4 h did not affect TSH-stimulated cAMP production, but TPA inhibited iodide organification in cells even in the presence of TSH or (Bu)2cAMP. Similarly NE and carbachol stimulated iodide organification in follicles but inhibited it in cells under basal as well as TSH-stimulated conditions. These effects of NE and carbachol were via alpha 2-adrenergic and muscarinic cholinergic receptors, respectively. However, NE and carbachol inhibited TSH-stimulated cAMP production in both follicles and cells. In thyroid cells, carbachol inhibited uptake and increased efflux of iodide within minutes. TPA also produced similar effects after longer periods of incubation, where an inhibition of uptake was seen by 1 h and an increase in efflux by 2 h. NE had a marginal inhibitory effect on uptake and had no effect on efflux of iodide. In contrast to these agents, TSH increased uptake but not efflux of iodide. The present results suggest that the response of the freshly isolated tissue to phorbol esters, NE and carbachol differs from that of cells in culture with respect to an important metabolic function of the thyroid gland. These agents seem to have direct effects on iodide transport and organification unrelated to their effects on cAMP production.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Effects of thyrotropin, carbachol, and protein kinase-C stimulators on glucose transport and glucose oxidation by primary cultures of dog thyroid cells.

Thyroid glucose metabolism can provide NADPH and H2O2 for thyroid hormone synthesis. Several agents stimulate glucose oxidation in thyroid slices, but little is known about glucose transport in this tissue. In the present study, various thyroid stimulators were tested on glucose transport and oxidation using primary cultures of dog thyroid cells. After preincubating the cells with the agonists, glucose uptake was measured by adding 2-deoxy-D-[1-3H]glucose [( 3H]2-DOG) for 5 min, and glucose oxidation was assessed during a single 60-min incubation with agonist and D-[1-14C]glucose. TSH (0.1-10 mU/ml), 12-O-tetradecanoyl phorbol-13-acetate (TPA; 10(-8)-10(-6) M), and carbachol 10(-6)-10(-2) M) stimulated [3H]2-DOG transport and glucose oxidation in a dose-dependent manner. The effect of TSH appears to be mediated by cAMP, since N6,2'-O-dibutyryl cAMP, 8-bromo-cAMP, cholera toxin, and isobutylmethylxanthine also stimulated [3H]2-DOG transport. Norepinephrine, which had no effect by itself on either transport or oxidation, inhibited TSH stimulation of [3H]2-DOG transport via an alpha 2-adrenergic receptor. The mechanism of the TPA and carbachol effect does not involve cAMP. A combination of maximal amounts of TSH or bromo-cAMP and carbachol or TPA produced additive effects on transport, while addition of TPA with carbachol produced no such additive effect. Kinetic analysis of 2-DOG transport indicated that all three agonists reduced the Km and increased the maximum velocity. Basal 2-DOG transport was increased in Ca2+-free medium, with or without EGTA, or in the presence of calcium channel blockers such as La3+ or Mn2+. In the presence of such increased basal glucose transport, TSH further stimulated it when Mn2+ was used, had no effect in Ca2+-free buffer plus EGTA, and caused an inhibition with La3+. Such inhibition was not caused when N6,2'-O-dibutyryl cAMP was used in the presence of La3+. Carbachol and TPA did not stimulate transport when the Ca2+ channel blockers were used, but a small increase was seen in Ca2+-free buffer containing EGTA. TSH stimulation of cAMP production was also diminished in the presence of La3+, but enhanced in the presence of Mn2+. The calmodulin inhibitor W-7 and the intracellular Ca2+ blocker 8-N,N-diethylamino octyl-3,4,5-trimethoxybenzoate hydrochloride diminished the stimulation of [3H]2-DOG transport and glucose oxidation induced by TSH, carbachol, and TPA. These data indicate that thyroid glucose transport and glucose oxidation are regulated by both cAMP-dependent and cAMP-independent systems.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Effects of thyroid-stimulating hormone, carbachol, norepinephrine, and adenosine 3',5'-monophosphate on polyphosphatidylinositol phosphate hydrolysis in dog thyroid slices.

TSH (10-250 mU/ml), carbachol (100 nM to 10 microM), and norepinephrine (10-100 microM) stimulated in a dose-dependent manner the accumulation of [3H]glycerophosphoinositol, [3H]inositol monophosphate, [3H]inositol bisphosphate, and [3H]inositol triphosphate in dog thyroid slices prelabeled with myo-[2-3H]inositol. The maximal effect of carbachol was considerably greater than that of TSH and norepinephrine. Carbachol stimulation of [3H]inositol phosphates (InsPs) was present by 5 min of incubation, while that of TSH required at least 30 min. Neither the basal level of [3H]InsPs nor the stimulation by carbachol (1 microM) or norepinephrine (500 microM) was affected by forskolin (10 microM) or cAMP analogs [8-bromo-cAMP or (Bu)2-cAMP; 1 mM]. A maximal amount of TSH (250 mU/ml) had ergistic effects on submaximal carbachol (1 microM)- and additive effects on maximal norepinephrine (500 microM)-induced accumulation of [3H]InsPs. Since not all of the effects of TSH on the thyroid can be explained by activation of the adenylate cyclase system, these data indicate that TSH may also regulate thyroid function through the polyphosphatidylinositol phosphate pathway. In addition, stimulation of the adenylate cyclase-cAMP system does not modify the effects of carbachol or norepinephrine on [3H]InsPs accumulation in dog thyroid slices.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Thyroid-stimulating hormone stimulates increases in inositol phosphates as well as cyclic AMP in the FRTL-5 rat thyroid cell line.

Studies were conducted to determine whether thyroid-stimulating hormone (TSH; thyrotropin), a hormone known to increase cytosol concentrations of cyclic AMP, also stimulates the formation of inositol phosphates in thyroid cells. TSH and noradrenaline both stimulated [3H]inositol phosphate formation in a concentration-dependent manner in the rat thyroid cell line, FRTL-5 cells, which had been prelabelled with [3H]inositol. The threshold concentration of TSH required to stimulate inositol phosphate formation was more than 20 munits/ml, which is approx. 10(3)-fold greater than that required for cyclic AMP accumulation and growth in these cells. We also demonstrate that membranes prepared from FRTL-5 cells possess a guanine nucleotide-activatable polyphosphoinositide phosphodiesterase, which suggests that activation of inositide metabolism in these cells may be coupled to receptors by the G-protein, Gp. Our findings suggest that two second-messenger systems exist to mediate the action of TSH in the thyroid.

Animals↗
PubMed1987

Multiple isoforms of ADP-ribosylated G-like proteins from mammalian thyroid membranes.

Bovine, canine, and porcine thyroid membrane proteins which were [32P] ADP-ribosylated by cholera and pertussis toxin in vitro were analyzed by one and two-dimensional polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. These three mammalian species have similar cholera toxin substrates (Mr 42,000 and 48,000) and pertussis toxin substrates (Mr 40,000). Resolution by two dimensional gel electrophoresis of these ribosylated proteins revealed that they each consist of at least 6 distinct polypeptides with similar isoelectric points ranging from approximately 5.5-7.0.

Adenosine Diphosphate Ribose↗
PubMed1987

Absence of hepatic extraction of gastric inhibitory polypeptide in conscious dogs.

Fractional hepatic extraction of gastric inhibitory polypeptide was examined in conscious unrestrained dogs with catheters in the portal vein, hepatic vein, and the carotid artery and Doppler flow probes on the portal vein and hepatic artery. Following a control period, endogenous gastric inhibitory polypeptide was stimulated by oral administration of glucose with and without prior infusion of atropine. In other experiments, gastric inhibitory polypeptide (20 ng/kg/min) was infused into the portal system in association with peripheral infusion of glucose. In none of these experiments was it possible to demonstrate any significant fractional hepatic extraction of gastric inhibitory polypeptide.

Animals↗
PubMed1987

Prevention of alpha 2-adrenergic inhibition on ADH action by pertussis toxin in rabbit CCT.

The present studies were performed to investigate the mechanism whereby alpha 2-adrenergic receptor occupancy inhibits the hydrosmotic action of antidiuretic hormone (ADH) in isolated cortical collecting tubules (CCT). The ADH-ribosyltransferase activity of pertussis toxin (PT) was used to promote covalent modification in CCT Ni, the inhibitory regulatory protein of adenylate cyclase, which presumably mediates the alpha 2-adrenergic inhibition of water flow. Tubules preincubated with PT were studied after the addition of ADH and then after the superimposition of clonidine. In these studies, the inhibition of Jv (water absorption, nl X mm-1 X min-1) and Pf (water permeability coefficient, cm/s), by the addition of 10(-4) M clonidine to the bath, was attenuated by PT in a concentration-dependent manner. Reversal of the inhibitory action of clonidine was accomplished with a concentration of 1.0 micrograms/ml PT. To further elucidate the molecular basis of Ni-mediated transduction of the alpha 2-adrenergic signal, ADP-ribosylation studies were undertaken in membrane preparations of dissected CCT segments. PT ADP ribosylated a 40,000 Mr peptide which was proportional to the amount of membrane protein added. Furthermore, pretreatment of CCT during dissection with 0.5 micrograms/ml PT dramatically decreased the susceptibility of the subunit of Ni (alpha i) to be subsequently ADP ribosylated by PT, when compared with CCT preparations not previously treated with PT. Cholera toxin ADP ribosylated a 42,000 Mr peptide from CCT membranes and PT pretreatment did not interfere with the reaction. We conclude that CCT segments have both the pertussis and cholera toxin substrates and the effect of clonidine to attenuate ADH action is mediated through Ni.

Adenosine Diphosphate↗
PubMed1987

First-pass hepatic extraction and metabolic effects of insulin and insulin analogues.

First-pass hepatic extraction of insulin and hepatic and peripheral contributions to hypoglycemia were compared in conscious dogs during portal infusion of insulin A1, B29 diacetyl insulin, or A1-B29 dodecoyl insulin at 7 and 14 pmol X kg-1 X min-1. The liver removed 43 +/- 2% of insulin, 12 +/- 1% of dodecoyl, and 8 +/- 1% of diacetyl insulin, in a single transhepatic circulation. The hypoglycemia induced by insulin and diacetyl insulin and the ensuing glucagon response were greater than that produced by the dodecoyl analogue. Diacetyl insulin primarily increased glucose utilization, dodecoyl insulin solely inhibited hepatic production, and insulin affected both. The lack of hepatic effect of diacetyl insulin during hypoglycemia can be ascribed to greater counterregulation, because under euglycemic clamp conditions, this analogue caused suppression of glucose production. The different patterns of hypoglycemia exhibited can be explained by the combined effects of altered distribution between the liver and peripheral tissues caused by differences in hepatic extraction, the effect of this phenomenon on the counterregulatory response, and the intrinsic biological potency of the analogues.

Animals↗
PubMed1987

Role of cellular Ca++ in phosphorylation of 21 K and 19 K polypeptides in cultured thyroid cells: effects of phorbol ester, trifluoperazine, and 8-diethylamino-octyl-3,4,5-trimethoxybenzoate hydrochloride.

Cultured dog thyroid cells contain 21 and 19 kilodalton (K) phosphoproteins which by several criteria have been identified as light chains of myosin (MLC). TSH causes a reduction in the phosphorylation state of the 21 K-19 K proteins, at least in part through activating adenylate cyclase and increasing cAMP levels. We now report that 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also decreases the 21 K-19 K protein phosphorylation state, but in contrast to that due to TSH, the TPA-induced decrease is not associated with elevated cAMP levels. The effect of TPA was not additive to that of TSH. Because Ca++ is a major factor regulating MLC kinase and TPA-stimulated protein kinase C in other systems, the role of Ca++ in the phosphorylation of the 21 and 19 K polypeptides in dog thyroid was examined. In intact cells, both (8-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8) (1 X 10(-4) M) and trifluoperazine (TFP) (4 X 10(-5) M) increase basal 21 K-19 K protein phosphorylation and inhibit the decrease in phosphorylation caused by TSH and TPA without affecting cAMP levels. Ionophore A23187 (5 X 10(-6) M) counteracts TMB-8- and TFP-stimulated phosphorylation as well as TMB-8 and TFP inhibition of TSH- and TPA-reduced 21 K-19 K phosphorylation. Incubation of 32PO4-labeled dog thyroid cells in the absence of extracellular Ca++ or with verapamil does not significantly affect basally phosphorylated 21 K-19 K proteins or the decreased 21 K-19 K phosphorylation state caused by TSH. These results strongly suggest that the phosphorylation state of the 21 and 19 K proteins is affected more significantly by intracellular Ca++ pools than by extracellular Ca++, and implicate a kinase(s) other than Ca++-calmodulin-dependent MLC kinase in the phosphorylation of MLC in the dog thyroid.

Animals↗
PubMed1987

Cloning and nucleotide sequence analysis of complementary deoxyribonucleic acid for bovine preproinsulin.

A cDNA library was prepared from poly(A+) RNA isolated from fetal bovine pancreas. Bacterial colonies were screened for sequences homologous to a rat preproinsulin I cDNA probe. Ten positive clones were selected at random and further studied. Northern blot analyses revealed that seven of these clones hybridized to a single RNA species, of approximately 400 nucleotides. Sequence analysis of one of these clones (pbI2885) revealed the entire structural region of bovine preproinsulin mRNA including a 72 nucleotide region encoding a signal peptide enriched in hydrophobic residues. The overall nucleotide homology between bovine and human preproinsulin mRNA was 76% for the preregion, 89% for the A chain, 83% for the B chain, and 68% for the C peptide (including a 15 nucleotide deletion).

Amino Acid Sequence↗
PubMed1987

Adenosine diphosphate ribosylation of G proteins by pertussis and cholera toxin in isolated membranes. Different requirements for and effects of guanine nucleotides and Mg2+.

ADP ribosylation of membranes by pertussis toxin (PT) and cholera toxin (CT) was studied as a function of addition of ATP, various guanine nucleotides, Mg2+, and inorganic phosphate (Pi). ADP ribosylation of a 40 kilodalton (kDa) band by PT is markedly enhanced by ATP and GTP and is strongly inhibited by Pi or Mg2+. GTP analogs (GTP gamma S and GMP-adenyl-5'-yl imidodiphosphate) were less effective. In contrast, ADP ribosylation of two substrates for CT (of 42 and 50 kDa) is stimulated by Pi, Mg2+, and GTP or GTP analogs such as GTP gamma S, but is unaffected by ATP. These stimulatory conditions correlate well with GTP-mediated activation of stimulated nucleotide-binding regulatory component of adenyl cyclase. Optimal conditions for ADP ribosylation by PT do not correlate simply with conditions thought to lead to stabilization of an inactive form of inhibitory nucleotide-binding regulatory component of adenyl cyclase (Gi) or Gi-like protein; rather, the data suggest the involvement of both a stimulatory nucleotide site on PT (positively affected by either ATP or GTP) and a stabilizing site on the PT substrate (affected by GDP, GDP beta S, or GTP). Treatment of membranes with Lubrol PX increased ADP ribosylation by PT by as much as 25- to 30-fold, but inhibited the action of CT. Using defined conditions for ADP ribosylation by PT and CT, distinct labeling patterns were observed in thyroid, brain, corpus luteum, liver, heart, and erythrocytes membranes. All membranes were more intensely labeled by PT rather than CT.

Adenosine Diphosphate Ribose↗
PubMed1987

Incubation of bovine thyroid slices with thyrotropin is associated with a decrease in the ability of pertussis toxin to adenosine diphosphate-ribosylate guanine nucleotide regulatory component(s).

Pretreatment of bovine thyroid slices with TSH resulted in desensitization of TSH-sensitive adenylyl cyclase activity but no change in stimulatory nucleotide binding regulatory component of adenylyl cyclase (Gs) activity assessed by reconstitution of the Gs-defective cyc-S49 adenylyl cyclase system. Possible changes in substrates for pertussis toxin (PT)-induced ADP ribosylation due to TSH treatment and/or in endogenous ADP ribosylation of membrane proteins were explored. Using 10 microM [32P]NAD+ as substrate, endogenous ADP ribosylation was not observed in membranes from control or TSH-treated slices. ADP ribosylation of alpha-subunits of Gs by cholera toxin was also unaffected by incubation of thyroid slices with TSH. In contrast, ADP ribosylation of 40 kilodalton (kDa) substrates for PT was decreased between 40% and 60% by TSH treatment. This effect of TSH was dependent on its concentration and the time of incubation of the slices and was specific for labeling of the 40 kDa PT substrate. Prostaglandin E1 treatment of thyroid slices, which results in a much smaller homologous desensitizing effect, did not result in changes in ADP ribosylation by PT. The effect of incubation of slices with TSH was abolished by pretreatment of the membranes with 0.3-1.0% Lubrol PX, which increased the labeling of the 40 kDa polypeptides. The data suggests that TSH induces in thyroid tissue a redistribution of 40 kDa polypeptides changing their availability to PT.

Adenosine Diphosphate Ribose↗
PubMed1987

Association of calmodulin with lysosomes.

We examined the subcellular localization of calmodulin in several cultured cells (primary thyroid follicular cells, thyroid C-cell tumour cells (TT), kidney cells (PtK2-L23) and peritoneal macrophages) by indirect immunofluorescence using affinity-purified antibody to calmodulin. When cells were fixed with 3% formaldehyde for 15 min prior to lysis with 0.5% Triton X-100, spindle fibres in mitotic cells were fluorescent and a diffuse cytoplasmic localization of calmodulin was observed in resting cells. However, when cells were lysed with 0.5% Triton X-100 for 90s prior to fixation for 30 min with 3% formaldehyde, three effects were observed. One: there was little diffuse cytoplasmic staining. Two: discrete vesicles were stained. Three: spindle fibres in mitotic cells were fluorescent. The stained vesicles were phase-dense and ranged from 0.1 to 0.5 micron in primary thyroid follicular cells but were smaller in PtK2 and TT cells. The thyroid follicular cells retained vesicular staining after exposure to thyrotropin and isobutylmethylxanthine, but the number of labelled vesicles decreased by almost 80%. Phase-dense vesicles were identified as lysosomes or other acidic vesicles by vital staining with Acridine Orange. After differential centrifugation of thyroid homogenates, calmodulin was measured by radioimmunoassay (RIA) and found in both cytosolic (89%) and membrane vesicle fractions (11%). The vesicular calmodulin was not eluted by washing with 5 mM-EGTA. The thyroid fractions were subjected to SDS-polyacrylamide gel electrophoresis and the gels incubated with 125I-labelled calmodulin to reveal calmodulin acceptor proteins (CAPs). The vesicle fraction contained quantitatively major CAPs with Mr of 200,000, 140,000, 89,000, 38,000 and 34,000, and minor CAPs of 60,000 and 50,000. Washing the pellet with 5 mM-EGTA did not reduce the content of CAPs. Thus, calmodulin and CAPs are present both in the cytoplasm and in a membrane vesicle fraction. The lysosomal locale of calmodulin and the effect of thyrotropin on vesicle number suggest a role for calcium in the regulation of lysosome function.

Animals↗
PubMed1986

Selective osmoreceptor dysfunction presenting as intermittent hypernatremia following surgery for a pituitary chromophobe adenoma.

Intermittent hypernatremia following hypothalamic surgery or trauma is usually attributed to the triphasic dysfunction of vasopressin release (diabetes insipidus, inappropriate vasopressin release, and diabetes insipidus). A 39-year-old patient had hypodipsia and intermittent hypernatremia following hypothalamic surgery for a chromophobe adenoma. Mean arterial pressure fell by 25 percent during orthostasis testing and was associated with an increase in vasopressin levels from 1.3 microU/ml to 12 microU/ml. Plasma renin activity and aldosterone increased from 1.1 to 16 ng/ml per hour and from 6.7 to 39 ng/dl, respectively, and remained elevated for three and a half hours after tilt testing. Hypertonic saline infusion, on the other hand, increased serum osmolality from 290 to 304 mOsm/kg but did not result in a significant rise in vasopressin levels (all were less than 1 microU/ml). These results are consistent with a selective dysfunction of the osmoreceptor pathways of vasopressin release and intact volume receptor-mediated pathways. Patients with intermittent hypernatremia following hypothalamic surgery or trauma should be questioned specifically regarding thirst. If it is impaired or absent, these patients should be watched carefully, not only for the development of triphasic dysfunction of vasopressin release, but also for a selective osmoreceptor dysfunction associated with thirst deficits as found in patients with "essential hypernatremia."

Adult↗