Search PubMed⌕ Search

Biomedical subjects

G L Robertson

Publications and source records attributed to G L Robertson.

At least 73 records · Page 4Linked to original sources
PubMed1984

Reduction of hypothalamic norepinephrine does not alter the osmoregulation of vasopressin in rats.

The supraoptic nuclei of the hypothalamus are known to be heavily innervated by noradrenergic neurons. However, the role of these neurons in regulating secretion of the antidiuretic hormone, arginine vasopressin, remains unsettled. In an effort to clarify this question, we studied the effect of multiple small doses of D,L alpha-methyl-p-tyrosine (alpha-MpT) on hypothalamic norepinephrine and the osmoregulation of vasopressin in rats. We found that, at the doses employed (80 mg/kg every 6 h for 24 h), alpha-Mpt reduced mean (+/- SD) hypothalamic norepinephrine by about 50% but did not affect plasma osmolality, sodium, glucose, urea, or vasopressin either under basal conditions or during osmotic stimulation by ip injection of hypertonic saline. During the latter, plasma vasopressin correlated directly with plasma osmolality and the regression lines that described the relationships in the control and drug-treated rats were identical. Hematocrit and mean arterial pressure were also unaffected by alpha-MpT. These findings do not support the concept based on previous studies that central noradrenergic pathways mediate the vasopressin response to osmotic stimuli.

Animals↗
PubMed1984

Hormonal abnormalities affecting sodium and water balance in acute respiratory failure due to chronic obstructive lung disease.

The pathogenesis of edema and hyponatremia associated with chronic obstructive lung disease (COLD) is poorly understood. In ten edematous COLD patients with acute respiratory failure (ARF), we monitored plasma renin activity (PRA), aldosterone (PA), and antidiuretic hormone (arginine vasopressin, AVP) for six days. Six patients receiving supplemental oxygen and antibiotics had near normal PRA, PA, and AVP, and diuresed Na+ and H2O and lost weight; only one patient was hyponatremic (PNa+ less than 130 mEq/L). On the same therapy, nonresponders (n = 4), with persistently elevated PRA, PA, and AVP, demonstrated no loss of Na+, H2O, or weight; three patients were hyponatremic. The PRA and PA correlated inversely with sodium loss; AVP correlated inversely with free water clearance. These studies suggest that in patients with COLD, edema, and ARF (1) lack of sodium diuresis may be contributed to by secondary hyperaldosteronism; and (2) hyponatremia can be explained by inappropriately elevated plasma AVP.

Arginine Vasopressin↗
PubMed1983

Abnormalities in plasma and cerebrospinal-fluid arginine vasopressin in patients with anorexia nervosa.

Previous studies have indicated that many patients with anorexia nervosa have defects in urinary concentration or dilution suggestive of abnormal secretion of the antidiuretic hormone arginine vasopressin. To explore this possibility, we examined the response of plasma vasopressin to intravenous hypertonic saline in anorexic patients before and after correction of their weight loss. We also measured basal levels of the hormone in the cerebrospinal fluid. In all four subjects studied before correction of weight loss, the response to hypertonic saline was abnormal: in one, the plasma level of arginine vasopressin increased subnormally relative to the plasma sodium level; in the other three, it fluctuated erratically, with no relation to plasma sodium. These defects persisted in the three patients studied three to four weeks after recovery of body weight. In two patients who were initially studied when they were underweight, the defects were gone six months after recovery; in five of seven other patients studied at least six months after recovery but not while they were underweight, the response was normal. Abnormalities in the osmoregulation of plasma arginine vasopressin were not accounted for by nonosmotic stimuli and were almost always associated with an absolute increase in the level of arginine vasopressin in the cerebrospinal fluid or a reversal of the normal (less than 1.0) cerebrospinal fluid/plasma ratio of arginine vasopressin. These results indicate that most if not all patients with anorexia nervosa have abnormal levels of arginine vasopressin in their plasma and cerebrospinal fluid that are corrected very slowly with weight gain. The cause and consequences of these abnormalities remain to be determined.

Adult↗
PubMed1983

Vasopressin response to orthostatic hypotension. Etiologic and clinical implications.

Plasma vasopressin was measured before and after tilt testing in 18 patients with orthostatic hypotension of various causes. In six patients, all of whom had normal osmotic regulation of vasopressin, normal stimulation of vasopressin did not occur on tilt testing; all six had clinical evidence of defects in the afferent or central connections of the baroregulatory reflex arc. In the remaining 12 patients, plasma vasopressin increased to levels appropriate for the degree of hypotension; none of these patients had clinical evidence of defects in afferent or central portions of the baroregulatory arc. Those with subnormal vasopressin response had significantly more severe orthostatic hypotension than the patients with normal vasopressin response, but none had plasma hypotonicity, an abnormality present in one-quarter of those with normal response. It is concluded that the vasopressin response to orthostatic hypotension may serve as a test of the integrity of the afferent and central components of the baroregulatory reflex arc. Furthermore, this study suggests that the normal vasopressin response to orthostatic hypotension may moderate the fall in blood pressure but may adversely affect water balance.

Adult↗
PubMed1983

Chronic hypernatremia from a congenital defect in osmoregulation of thirst and vasopressin.

An infant with microcephaly and delayed development was found to have chronic asymptomatic hypernatremia. Computerized brain tomography disclosed dysplasia of the midline structures, septum pellucidum and corpus collosum. Evaluation revealed defective osmoregulation, hypothalamic hypothyroidism, and hypogonadotropinism. He showed no desire to drink at plasma osmolalities over 330 mOsm/kg. His plasma vasopressin levels (less than or equal to 1.4 pg/ml) were inappropriately low relative to his high levels of plasma osmolality (greater than or equal to 310 mOsm/kg), which might be accounted for by either deficient neurohypophyseal vasopressin stores or disturbance of the hypothalamic osmoreceptors governing vasopressin. The first possibility was ruled out by demonstrating normal vasopressin response (167 pg/ml) to nonosmotic (emetic) stimulation. Under baseline conditions, his urine was concentrated up to 747 mOsm/kg and urine volume was low. With water loading, maximal water diuresis developed (urine osmolality 68 mOsm/kg), but his plasma osmolality remained in the hyperosmolar range (312 mOsm/kg). Treatment with a vasopressin analogue, desamino-D-arginine vasopressin, and forced hydration restored plasma osmolality and plasma sodium to normal. These findings indicate a severe defect in the hypothalamic osmoreceptors controlling thirst and vasopressin secretion with normal vasopressin stores and preserved vasopressin responsiveness to nonosmotic stimuli. To our knowledge, this report provides the first documentation of selective osmoreceptor defect in conjunction with congenital dysplasia of midline brain structures.

Brain↗
PubMed1983

Inappropriate vasopressin secretion (SIADH) in burned patients.

To determine if concentration of plasma arginine vasopressin (AVP) is inappropriate for the plasma Na+ concentration in hyponatremic burned patients, we obtained 32 plasma samples from 20 patients with total burn size (TBS) 15 to 80% of body surface on or after postburn day (PBD) 4 in the morning following all-night recumbency. In the 25 samples (17 patients) with hyponatremia, AVP was elevated, 1.6 to 14.3 (normal less than 0.5) pg/ml. Most patients with normal serum Na+ had normal AVP values. Out of the total, nine patients (12 samples) without renal failure or sepsis, selected also for hyponatremia and urinary Na+ greater than or equal to 20 mEq/L, were considered separately. BUN of 11.7 +/- 1.8 mg/dl and plasma glucose of 130 +/- 5.6 mg/dl, Na+ of 130 +/- 1.1 mEq/L, calculated osmolality of 272 +/- 1.6 mosm/kg, and cortisol of 20.4 +/- 1.6 micrograms/dl were associated with a 24-hour fluid intake of 4.3 +/- 0.26 L and urinary output of 2.7 +/- 0.33 L, Na+ of 80 +/- 14 mEq/L, and osmolality of 520 +/- 73 mosm/kg (mean +/- SE). In all of the plasma samples, AVP was markedly elevated (6.9 +/- 1.1 pg/ml). In another study, four hyponatremic burned patients were given a standard water load. Excretion of the water was delayed, and further dilution of the initially hypotonic plasma resulted in a fall of urinary osmolality and plasma AVP. Cutaneous thermal injury can cause resetting of the mechanism linking plasma tonicity and AVP secretion resulting in dilutional hyponatremia. This syndrome occurs in the absence of gross physiologic perturbations such as volume depletion or adrenal insufficiency.

Adolescent↗
PubMed1983

Osmoregulation of thirst and vasopressin secretion in human subjects: effect of various solutes.

Various hypertonic solutions were infused in healthy human volunteers to determine their effect on thirst and vasopressin secretion. Hypertonic saline and mannitol produced prompt and parallel increases in plasma osmolality and vasopressin concentration. For both of these solutes, there was a high degree of correlation between these measurements. The slope describing this relationship varied considerably between individuals, but the same subjects showed similar slopes with either saline or mannitol. Both solutions stimulated thirst. Hypertonic urea infusions produced a comparable rise in osmolality but produced a smaller increase in plasma vasopressin and stimulated thirst in only one of the subjects. With urea, the correlation between plasma osmolality and vasopressin was significantly lower. Within individuals, the slope describing this relationship was significantly correlated with that seen during hypertonic saline. Hypertonic glucose significantly increased plasma osmolality but decreased plasma vasopressin and had no detectable effect on thirst. We conclude that osmoregulation of vasopressin in humans is mediated by a selective osmoreceptor that is located primarily outside of the blood-brain barrier and that individual differences in osmoregulatory sensitivity are not solute specific.

Adult↗
PubMed1983

The effect of lithium on the osmoregulation of arginine vasopressin secretion.

The effect of lithium on the plasma arginine vasopressin (AVP) response to the iv infusion of 5% saline was determined in six patients with primary effective disorder. Lithium did not significantly affect baseline weight, plasma osmolality, sodium, or AVP levels. However, lithium significantly increased the mean rate of change or the sensitivity of the plasma AVP response to the osmotic stimulus (from 0.42 +/- 0.17 to 1.08 to 0.24 pg/ml/mosmol/kg; P less than 0.025, by paired t test). This change was associated with a slight but significant increase in the precision of the response, as reflected in the correlation coefficient, but there was no difference in the calculated intercept or osmotic threshold for AVP secretion. This study indicates that patients on lithium do not, as previously suggested, show partial central diabetes insipidus. Rather, AVP secretion seems to be enhanced. Moreover, the mechanism of this enhancement is a specific increase in the sensitivity of the osmoreceptor rather than a lowering of the osmotic threshold for AVP secretion. The effect of lithium cannot be clearly accounted for by any of the physiological variables known to influence the sensitivity of the system and is probably due to an effect of the drug on the level or activity of neuromodulators which influence the function of hypothalamic osmoreceptors.

Adult↗
PubMed1983

Carbamazepine diminishes the sensitivity of the plasma arginine vasopressin response to osmotic stimulation.

Carbamazepine, a drug used to treat manic-depressive illness, has been reported to possess antidiuretic properties, but its effects on arginine vasopressin (AVP) secretion are controversial. Consequently, we examined plasma AVP secretion during hypertonic (5%) saline infusion in seven manic-depressive patients while on placebo and after 3-5 weeks of carbamazepine treatment. We also measured carbamazepine's effects on basal levels of the hormone in cerebrospinal fluid. Carbamazepine significantly reduced the sensitivity of the plasma AVP response to osmotic stimulation without affecting the osmotic threshold for AVP secretion. Moreover, carbamazepine did not affect baseline weight, plasma osmolality, plasma sodium, urine output, plasma AVP, or cerebrospinal fluid AVP. Although the functional significance of these findings remain to be fully determined, the fact that carbamazepine significantly reduced AVP secretion without inducing diuresis supports previous suggestions that carbamazepine enhances renal responsivity to available AVP. In addition, since carbamazepine failed to affect the osmotic threshold, the reported cases of carbamazepine-induced inappropriate AVP secretion and water intoxication must be very uncommon and probably represent idiosyncratic responses.

Arginine Vasopressin↗
PubMed1982

Neurogenic disorders of osmoregulation.

The osmolality of body fluids is normally maintained within a narrow range. This constancy is achieved largely via hypothalamic osmo-receptors that regulate thirst and arginine vasopressin, the antidiuretic hormone (ADH). Anything that interferes with the full expression of either osmoregulatory function exposes the patient to the hazards of abnormal increases or decreases in plasma osmolality. Hyposmolality is almost always due to a defect in water excretion. Increased intake may contribute to the problem but is rarely, if ever, a sufficient cause. Impaired water excretion can be due to a primary defect in the osmoregulation of ADH (inappropriate antidiuresis) or secondary to nonosmotic stimuli like hypovolemia or nausea. The two types differ in clinical presentation and treatment. Resetting of the ADH osmostat is commonly associated with resetting of the thirst osmostat. Hyperosmolarity is almost always due to deficient water intake. Excessive excretion may contribute to the problem but is never a sufficient cause. Impaired water intake can result from a defect in either the osmoregulation of thirst of the necessary motor responses. Thirst may be deficient because of primary osmoreceptor damage as in the syndrome of adipsic hypernatremia or secondary to nonosmotic influences on the set of the system. They are distinguishable by the clinical presentation as well as the type of ADH defects with which they are associated. So-called essential hypernatremia due to primary resetting of the osmostat has been postulated, but unambiguous evidence for such an entity has not yet been reported.

Body Water↗
PubMed1982

Radioimmunoassay of vasopressin in familial cental diabetes insipidus.

We examined plasma arginine-vasopressin concentrations by radioimmunoassay in two brothers, aged 6 and 7.5 years, with familial central diabetes insipidus inherited as an autosomal dominant trait. Plasma AVP was measured in relation to increasing plasma osmolality induced by water deprivation and hypertonic saline infusion. The brother with the more severe urinary concentrating defect had no detectable AVP when his plasma osmolality was as high as 306 mOsm/kg; the other brother had detectable but clearly subnormal AVP concentrations. The one brother tested had an apparently normal end-organ response to exogenous vasopressin. Chlorpropamide had a significant antidiuretic effect in the brother with detectable AVP levels, and a lesser effect in the other brother . Our findings suggest that intrafamilial variation in the severity of congenital DI is related to the degree of vasopressin deficiency.

Arginine Vasopressin↗
PubMed1982

Age-related failure of volume-pressure-mediated vasopressin release.

Osmoreceptor sensitivity, as estimated by the plasma vasopressin (AVP) response to hypertonic saline infusion, increases with age. We studied volume-pressure sensitivity, as estimated by the plasma AVP response to orthostasis, in healthy young (19-31 yr old; n = 12) and old (62-80 yr old; n = 15) subjects. After remaining recumbent overnight (minimum of 8 h), subjects stood quietly for 8 min. Cardiovascular changes on standing were not influenced by age. The peak plasma AVP response was greater in the young than in the old (P = 0.02, by rank sum test). When categorized as responders (peak AVP response, greater than or equal to 3 pg/ml) or nonresponders (peak response, less than 3 pg/ml), the young group included 11 responders and 1 nonresponder, while the old group included 8 responders and 7 nonresponders (P = 0.03, by Fisher exact test). There was no difference in the marked increase in plasma norepinephrine on standing between old responders (n = 6) and old nonresponders (n = 4). These studies indicate that failure to release AVP in response to orthostasis is more common in the elderly than in the young. The intact norepinephrine response to orthostatis in the elderly, regardless of the AVP response, suggests that the age-related defect is distal to the vasomotor center in the afferent limb of the baroreceptor reflex arc. Insensitivity to the volume and pressure changes accompanying hypertonic saline infusion may contribute to the previously noted augmented AVP response of the elderly to hyperosmolality.

Adult↗
PubMed1982

Abnormalities of sodium and H2O handling in chronic obstructive lung disease.

The pathogenesis of edema and hyponatremia in chronic obstructive lung disease (COLD), is poorly understood. Previously, in nonedematous patients with hypercapnia, small increases in plasma renin activity occurred, which prompted this study. In 25 hypercapnic, edematous, often hyponatremic patients with COLD, we measured renal hemodynamics, H2O, and sodium (Na+) excretion, plasma levels of renin activity (PRA), plasma levels of aldosterone (PA), and the plasma arginine vasopressin (AVP)-osmolality relationship. A high prevalence of elevated PRA, PA, and AVP levels excessively high for plasma osmolality was observed. Elevated PRA and Pa correlated with the inability to excrete Na+; an elevated AVP level correlated with the inability to excrete H2). These data suggest that, in conjunction with the hypercapnia-hypoxia-mediated disturbance in renal function, stimulation of the renin-aldosterone level and of the AVP systems contributes, respectively, to edema formation and to hyponatremia in advanced COLD.

Aldosterone↗
PubMed1981

A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria.

The diagnoses provided by a standard indirect test of vasopressin function were compared with those obtained by radioimmunoassay of plasma vasopressin in 24 patients with nonglucosuric polyuria. All seven cases of severe neurogenic diabetes insipidus diagnosed by the indirect tests were confirmed by the vasopressin assay. However, two of six patients with partial neurogenic diabetes insipidus by indirect criteria had normal vasopressin secretion by the direct assay; one was found to have primary polydipsia, and the other nephrogenic diabetes insipidus. Moreover, three of 10 patients diagnosed as having primary polydipsia by the indirect test had clear evidence of partial vasopressin deficiency by the direct assay. The inability of the indirect test to distinguish accurately between partial neurogenic diabetes insipidus and primary polydipsia may be explained by increased sensitivity to low concentrations of vasopressin in the former disorder and a reduction of maximal concentrating ability in both. We conclude that the incorporation of a vasopressin assay improves accuracy in the differential diagnosis of polyuria.

Adolescent↗