The Antidiuretic Effect of Chronic Hydrochlorothiazide Treatment in Rats with Diabetes Insipidus: Renal Mechanisms

Shirley, DG; Walter, S. J.; Laycock, John

doi:10.1042/cs0630533

Cited by 39 publications

(24 citation statements)

References 14 publications

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“…Previously, the osmolality of renal papillary interstitial fluid from HCTZ-treated Brattleboro rats was shown to be considerably greater than that from untreated animals, accompanied by a significant increase in sodium concentration (9). In this study, the abundance of NCC in distal convoluted tubule was not altered by Li administration but increased by HCTZ treatment in Li-induced NDI rats.…”

Section: Hctz Treatment Upregulates Ncc and Enac In Liinduced Ndimentioning

confidence: 48%

“…However, Shirley et al (9) showed that the mechanism of sustained antidiuresis during chronic HCTZ administration in DI differs from that of the acute response. When they recorded distal delivery and urine flow simultaneously during chronic thiazide antidiuresis, the allover change in distal delivery (Ϫ15%) or the enhanced proximal solute and water reabsorption was considered to be too small to account for the profound antidiuresis.…”

Section: Hctz Treatment Partially Reverses Li-induced Aqp2 Downregulamentioning

confidence: 99%

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Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Kim

Lee²,

Oh³

et al. 2004

Journal of the American Society of Nephrology

133

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Abstract. Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na ϩ concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na ϩ transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry. After feeding male Sprague-Dawley rats Li chloride-containing rat diet for 4 wk, HCTZ or vehicle was infused subcutaneously via osmotic minipump. Urine output was significantly decreased by HCTZ treatment, whereas it was not changed in vehicle-treated rats. Urine osmolality was also higher in HCTZ-treated rats than in vehicle-treated rats. Semiquantitative immunoblotting using whole-kidney homogenates revealed that HCTZ treatment caused a significant partial recovery in AQP2 abundance from Li-induced downregulation. AQP2 immunohistochemistry showed compatible findings with the immunoblot results in both cortex and medulla. The abundances of thiazide-sensitive NaCl co-transporter and ␣-epithelial sodium channel were increased by HCTZ treatment. Notably, HCTZ treatment induced a shift in molecular weight of ␥-epithelial sodium channel from 85 to 70 kD, consistent with previously demonstrated aldosterone stimulation. The upregulation of AQP2 and distal renal Na ϩ transporters in response to HCTZ treatment may account for the antidiuretic action of HCTZ in NDI.In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite normal or elevated concentrations of the antidiuretic hormone arginine vasopressin. The acquired form of NDI is much more common than the congenital form, which has mutations either in the vasopressin V 2 receptor gene or in the aquaporin-2 (AQP2) gene (1). Lithium (Li) treatment (2), hypokalemia (3), and ureteral obstruction (4) are three common causes of acquired NDI, and all have been associated with downregulation of AQP2 (2-4).One of the recommended regimens for the treatment of NDI is low-sodium diet coupled with thiazides, although amiloride is preferably used to mitigate Li-induced polyuria in humans because of its blunting the inhibitory effect of Li on water transport in the collecting duct (5). Thiazide diuretics paradoxically decrease urine volume and increase urine osmolality presumably by producing a mild sodium depletion (6). The widely accepted hypothesis suggests that thiazide-induced sodium depletion causes a reduction in distal delivery associated with enhanced fractional water reabsorption in the collecting duct (6,7). However, the mechanism by which thiazide diuretics produce their paradoxic antidi...

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Section: Hctz Treatment Upregulates Ncc and Enac In Liinduced Ndimentioning

confidence: 48%

Section: Hctz Treatment Partially Reverses Li-induced Aqp2 Downregulamentioning

confidence: 99%

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Kim

Lee²,

Oh³

et al. 2004

Journal of the American Society of Nephrology

133

View full text Add to dashboard Cite

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“…the LE rats in experiment 1) rmP induced a small diuresis, which was converted into an antidiuresis in the absence (or suppression) of circulating vasopressin. These findings are reminiscent of the paradoxical, and still not completely understood, antidiuretic effect of thiazide diuretics in diabetes insipidus (26,27).…”

Section: Discussionmentioning

confidence: 90%

Renal effects of recombinant prolactin in anaesthetized rats

Morrissey

Newth

Rees

et al. 2001

European Journal of Endocrinology

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Objective: To re-examine the controversial possibility that prolactin exerts renal effects, using recombinant mouse prolactin (rmP), in the presence and absence of circulating vasopressin. Design: In experiment 1, the renal effects of rmP were examined in anaesthetized Brattleboro rats with hereditary hypothalamic diabetes insipidus (BDI) lacking circulating vasopressin and normal animals of the parent Long Evans (LE) strain. In experiment 2, salt and water excretion were studied in fluidloaded normal Sprague±Dawley (SD) rats, some of which received rmP. Methods: In experiment 1, BDI and LE rats maintained in fluid balance were infused i.v. with each of three concentrations of rmP (10, 20 and 40 mg/ml per h) or maintained on 150 mmol/l NaCl vehicle (controls). In experiment 2, the SD rats were infused with 75 mmol/l NaCl in order to induce a state of diuresis comparable to that of BDI rats, some of them then receiving the rmP i.v. Results: A profound rmP-induced dose-dependent decrease in urine excretion P , 0X005 and a lesser decrease in sodium excretion in the BDI rats was in marked contrast with the small but significant increase in urine excretion in the LE rats compared with controls P , 0X025X The rmPinfused fluid-loaded SD rats also demonstrated a significant P , 0X05 dose-related antidiuresis compared with the control animals, in addition to a decrease in sodium excretion. Conclusions: These results show that prolactin has a profound antidiuretic effect in the absence of circulating vasopressin. In contrast, when vasopressin is present in the circulation rmP has a small, but opposite, diuretic effect. Thus the use of a recombinant prolactin has provided evidence for renal effects of this hormone which are modified in the presence of the circulating neurohypophysial hormone vasopressin.

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“…Following micropuncture, the kidney papilla was excised and a sample of papillary interstitial fluid obtained (Shirley, Walter & Laycock, 1982). Although urine osmolality was lower in thiazide-treated rats than in control animals (1377+64 vs. 1885 + 150 m-osmole/kg H20, P < 0 005), papillary fluid osmolality in the two groups was similar (thiazide group: 1867 + 162; control group: 1732 + 106 m-osmole/ kg H20).…”

Section: Pmentioning

confidence: 99%

Proceedings of the Physiological Society, 20‐21 December 1982, Birmingham Meeting: Communications

Cervero

Schouenborg²,

Sjölund

et al. 1983

The Journal of Physiology

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Most skeletal muscles are attached through tendons, the elastic properties of which have a significant effect on their activity. Only those parts of a tendon which lie outside the body of a muscle can be subjected to normal mechanical testing, but tendinous fibres extend into many muscles, and their lengths may far exceed the muscle fibres themselves. In this paper we describe a method of measuring the stiffness of the entire tendinous attachment of the cat's soleus muscle.Muscle spindles are used as indicators of muscle fibre length. Spindles are very sensitive to changes in muscle length, but their afferents become silent when the muscle contracts and this silence is attributed to unloading of the spindles as muscle fibres shorten at the expense of their tendinous attachments.We have sinusoidally stretched the muscle-tendon combination while sinusoidally modulating the frequency of the stimulus to the muscle fibres. We have then adjusted movement and stimulus until their effects on the muscle spindle offset each other, so that the afferent activity from the muscle spindle was no longer modulated by the movement. In this null situation, we assume that the muscle fibres were remaining at constant length, and that all the imposed movement was taken up in the tendinous attachments. Measurements of the movement and of the force necessary to sustain it would then give a value for the stiffness of the tendon alone. By adjusting the parameters of muscle stimulation, we determined this stiffness for different mean forces of contraction.Cats were anaesthetized with pentobarbitone sodium and recordings were made from the primary afferent fibres of soleus while the tendon was subjected to sinusoidal movement of small amplitude (up to 02 mm) at a frequency of about 2 Hz. The ventral nerve roots that supplied soleus were split into four or five divisions, and the muscle was activated by stimulating the divisions in sequence to obtain smooth contractions with low stimulus rates (Rack & Westbury, 1969). The rate of stimulation was then modulated sinusoidally about a mean level, and the mean rate, the depth and the phase of modulation were varied in relation to the movement until the modulation of the afferent discharge from the muscle spindles was minimized.Measurements indicated that the tendon behaves as an elastic structure with a stiffness that is related to the force of contraction, varying between 2 N/mm at low forces and 20 N/mm at high forces. Soleus muscles of young rats are composed of two types of motor units -slow ones, and fast fatigue-resistant ones. Thus they have two populations of motoneurones that supply the muscle. Disconnecting motoneurones from the soleus muscle by nerve crush at birth leads to death of a proportion of motoneurones (Romanes, 1946; Zelenai & Hnik, 1963). In this study we investigated which of the two types of motoneurones is more resistant to nerve injury. In addition we assessed the size of the peripheral field of the surviving motoneurones and their size.The sciatic nerve of newborn ra...

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The Antidiuretic Effect of Chronic Hydrochlorothiazide Treatment in Rats with Diabetes Insipidus: Renal Mechanisms

Cited by 39 publications

References 14 publications

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Antidiuretic Effect of Hydrochlorothiazide in Lithium-Induced Nephrogenic Diabetes Insipidus Is Associated with Upregulation of Aquaporin-2, Na-Cl Co-transporter, and Epithelial Sodium Channel

Renal effects of recombinant prolactin in anaesthetized rats

Proceedings of the Physiological Society, 20‐21 December 1982, Birmingham Meeting: Communications

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