Cheryl Ray

Serial measures of plasma homocyst(e)ine after acute myocardial infarction.

To determine whether plasma levels of homocyst(e)ine are affected by the acute phase response, we studied 10 subjects serially after acute myocardial infarction. Our data indicate that measurement of homocyst(e)ine in patients with myocardial infarction should ideally be deferred for 7 days if spuriously low levels are to be averted.

ACUTE EFFECT OF ETHANOL ON RENAL ELECTROLYTE TRANSPORT IN THE RAT

1. Despite human and animal studies, the direct effect of ethanol on renal water and electrolyte transport is poorly understood. The acute effect of increasing plasma concentrations of ethanol was evaluated in a water diuretic anaesthetized rat model which inhibits endogenous arginine vaso‐pressin (AVP) release.

A study of the interaction of catecholamines and antidiuretic hormone on water permeability and the cyclic AMP system in isolated papillae of the rat.

The diffusional water permeability of collecting ducts in vitro and the cyclic A.M.P. content of isolated papillae were measured after exposure to different concentrations of antidiuretic hormone, isoproterenol and noradrenalin. Antidiuretic hormone 25 μ units/ml. caused a 25% increase in diffusional water permeability. This response was not affected by isoproterenol (10−6 M) or noradrenalin (2 ×10−6 M). Antidiuretic hormone 100 μ unit ml−1 caused a 50% increase in diffusional water permeability which likewise was not altered by isoproterenol or noradrenalin. Isoproterenol (10−6 M) and noradrenalin (2×10−6 M) had no significant effect on basal levels of diffusional water permeability.Isoproterenol had no significant effect on the tissue concentration of cyclic A.M.P. or on the increase in cyclic A.M.P. concentration induced by antidiuretic hormone. Noradrenalin (2×10−6 and 10−4) had no significant effect on basal cyclic A.M.P. concentration. However, noradrenalin inhibited the stimulation of cyclic A.M.P. induced by antidiuretic hormone. This effect was inhibited by phentolamine.This study suggests that catecholamines do not alter water handling by a direct action on the water permeability of the kidney but probably exert their action through an effect of A.D.H. release.

THE EFFECT OF ADRENALECTOMY ON WATER PERMEABILITY IN RAT PAPILLARY COLLECTING DUCT

1. Chronic adrenal insufficiency impairs maximal urine concentration, probably in part due to reduced medullary tonicity but also possibly by inhibition of distal nephron water transport. This latter defect has been demonstrated in rabbit but not in rat.

THE MECHANISM OF POLYURIA IN RATS PRETREATED WITH LITHIUM STUDIES BY IN VITRO MICROPERFUSION

The collecting ducts in papillae taken from normal rats have a measurable increase in diffusional tritiated water (THO) permeability with ADH 5 μunit/ml and this increase is maximal with antidiuretic hormone (ADH) 100 μunit/ml added to the media.

The effect of prostaglandin E2 and ADH on diffusional water permeability in the collecting duct of an isolated rat papilla

The effect of prostaglandin on diffusional water permeability has been studied in collecting ducts in an isolated rat papilla. PGE2 increased water permeability. The effect was significant at a concentration of 10−8 mol l−1 and was maximal with a concentration of 10−6 mol l−1. The maximal increment of 0.94±0.10 (SEM) μm s−1 was approximately half that produced by maximal stimulation with antidiuretic hormone (2.18±0.12 μm s−1).A concentration of 10−8 mol l−1 produced an increase in basal water permeability and 25 μunit ml−1 ADH, which without PGE2 present gave a similar increase, had no incremental effect. ADH 100 μunit ml−1 increased permeability to a value similar to that observed in the absence of PGE2. Thus PGE2 and ADH both increase water permeability but the increments are not additive.Indomethacin in a concentration that inhibited prostaglandin production altered the response of the collecting duct to ADH. The dose response curve was shifted to the left and the maximal increase in water permeability and the lowest dose at which a response occurred took place at concentrations less than 1/2 those required in its absence.Prostaglandins influence the action of ADH and it is likely that in life they regulate and modulate the change in water permeability induced by anti-diuretic hormone.

ACUTE EFFECT OF PHYSIOLOGICAL CONCENTRATIONS OF VASOPRESSIN ON RAT RENAL FUNCTION

1. The antidiuretic, pressor and electrolyte transport effects of arginine vasopressin (AVP) were simultaneously evaluated in the anaesthetized water diuretic rat. Increasing concentrations of AVP (7.5, 75 and 750 ng/kg bolus and per h), were used to produce plasma levels which approximate the physiological range (4.8 ± 2.4, 35.7 ± 12.5, 85.2 ± 16.1 pg/mL respectively).

THE PERMEABILITY OF COLLECTING DUCTS TO 22Na+ AND 36CI− IN RAT ISOLATED PAPILLAE

1. The diffusional permeability of collecting ducts to 22Na+ and 36CI− was measured in rat papillae in vitro.

A CIRCULATING PLASMA FACTOR THAT INHIBITS THE ACTION OF ANTIDIURETIC HORMONE

Publisher Summary This chapter discusses studies which indicate that in the plasma of rats pre-treated with lithium or made hypokalemic, there is a factor that inhibits the effect of antidiuretic hormone (ADH) on diffusional water permeability. The inhibition appears to be a competitive inhibition as the maximum response is obtained with a higher concentration of ADH. Plasma itself appears to increase the sensitivity of the tissue to ADH and increments in water permeability is detected with ADH concentrations close to the physiological range. Whether a similar inhibiting factor is present in the plasma from hypercalcemic rats cannot be stated as Ca2+ itself have an effect on the response to ADH and this effect has not been excluded. Lithium inhibits sodium transport out of cells and thereby causes alterations in cellular potassium concentration. It is possible that high plasma lithium levels and hypokalemia stimulate the production of a circulating factor by a similar mechanism. Changes in prostaglandins somatostatin or the presence of an unidentified peptide may be the cause of this effect.

Effect of Diuretics on Sodium and Chloride Permeability in the Rat Papillary Collecting Duct

While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 ± 0.05 compared with 0.83 ± 0.08 µm/s), although both were relatively impermeable when compared to water. Furosemide (10–4) and hydrochlorothiazide (10–3) both increased the diffusional permeability of chloride by approximately 30% (0.80 ± 0.06 to 1.04 ± 0.09 µm/s, p < 0.01, and 0.74 ± 0.09 to 0.98 ± 0.10 µm/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4°C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10–4) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.