Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney

Beck, Nama; Sk, Webster

doi:10.1152/ajplegacy.1976.231.4.1204

Cited by 35 publications

(28 citation statements)

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(3 reference statements)

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“…Although the mechanisms by which hypokalemia causes nephrogenic diabetes insipidus are a matter of contention, it appears to be due to a reduction in the production of cAMP (the second messenger for vasopressin action) in response to vasopressin, either by direct inhibition of adenylate cyclase (2,16,25) or via increased prostaglandin production (14). Our previous observation that lithium causes a decrease in AQP2 expression could also be explained by this mechanism, as the lithium-induced polyuria is thought to be due to an inhibition of adenylate cyclase (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…Prolonged hypokalemia causes substantial morphological change in kidney ultrastructure, and is associated with renal functional abnormalities, including a vasopressin-resistant decrease in urinary concentrating ability (1). The rat provides a good animal model of these effects, with changes similar to those seen in human kidney (2).…”

Section: Introductionmentioning

confidence: 99%

“…While hypokalemia has been associated with increased prostaglandin production (13)(14)(15), and inhibitors of prostaglandin synthesis restore the responsiveness of rabbit isolated perfused collecting ducts to vasopressin (14), prostaglandins do not appear to be an important factor in the etiology of hypokalemia-induced polyuria in rats (16). In the rat, there may be a decrease in adenylate cyclase sensitivity in response to vasopressin (2,17), thus reducing production of cAMP, the second messenger for vasopressin action. In addition to inhibiting the acute vasopressin-induced increase in water permeability, this decrease in cAMP may also be the messenger causing a decrease in AQP2 expression.…”

Section: Introductionmentioning

confidence: 99%

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Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

Marples¹,

Frøkiær²,

Dørup³

et al. 1996

J. Clin. Invest.

274

157

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Prolonged hypokalemia causes vasopressin-resistant polyuria. We have recently shown that another cause of severe polyuria, chronic lithium therapy, is associated with decreased aquaporin-2 (AQP2) water channel expression (Marples, D., S. Christensen, E.I. Christensen, P.D. Ottosen, and S. Nielsen, 1995. J. Clin. Invest. , 95: 1838-1845). Consequently, we studied the effect in rats of 11 days' potassium deprivation on urine production and AQP2 expression and distribution. Membrane fractions were prepared from one kidney, while the contralateral kidney was perfusion-fixed for immunocytochemistry. Immunoblotting and densitometry revealed a decrease in AQP2 levels to 27 Ϯ 3.4% of control levels ( n ϭ 11, P Ͻ 0.001) in inner medulla, and 34 Ϯ 15% of controls ( n ϭ 5, P Ͻ 0.05) in cortex. Urine production increased in parallel, from 11 Ϯ 1.4 to 30 Ϯ 4.4 ml/day ( n ϭ 11, P Ͻ 0.01). After return to a potassium-containing diet both urine output and AQP2 levels normalized within 7 d. Immunocytochemistry confirmed decreased AQP2 labeling in principal cells of both inner medullary and cortical collecting ducts. AQP2 labeling was predominantly associated with the apical plasma membrane and intracellular vesicles. Lithium treatment for 24 d caused a more extensive reduction of AQP2 levels, to 4 Ϯ 1% of control levels in the inner medulla and 4 Ϯ 2% in cortex, in association with severe polyuria. The similar degree of downregulation in medulla and cortex suggests that interstitial tonicity is not the major factor in the regulation of AQP2 expression. Consistent with this furosemide treatment did not alter AQP2 levels. In summary, hypokalemia, like lithium treatment, results in a decrease in AQP2 expression in rat collecting ducts, in parallel with the development of polyuria, and the degree of downregulation is consistent with the level of polyuria induced, supporting the view that there is a causative link. ( J. Clin. Invest.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

Marples¹,

Frøkiær²,

Dørup³

et al. 1996

J. Clin. Invest.

274

157

View full text Add to dashboard Cite

show abstract

“…Earlier studies using heterogenous kidney tissue preparations from KD rats showed a defect in ADH-stimulated adenylate cyclase activity and cyclic adenosine-3',5'-monophosphate (cAMP) accumulation in the medullary and papillary regions of the kidney (9,10 (12). Although these studies and ones in amphibian urinary bladders (13) indirectly suggest that an impaired hydroosmotic response to ADH exists in KD animals, the exact location along the nephron and the underlying mechanism responsible for the urinary concentrating defect remain to be shown conclusively.…”

Section: Introductionmentioning

confidence: 99%

In vivo and in vitro studies of urinary concentrating ability in potassium-depleted rabbits.

K¹,

Davidson²,

McKinney³

1985

J. Clin. Invest.

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The factors responsible for the urinary concentrating defect associated with the potassium-depleted (KD) state are uncertain. The present studies were designed to, first, determine whether a urinary concentrating defect exists in potassium-depleted rabbits and, second, to use the technique of in vitro perfusion to evaluate directly the antidiuretic hormone (ADH) responsiveness of cortical collecting tubules (CCT) in this setting.Feeding female New Zealand White rabbits a potassiumdeficient diet for 2 wk caused a significant fall in plasma potassium levels in both the ad-libitum and controlled water intake groups (P < 0.001). Muscle potassium content after 2 wk of potassium restriction fell from 45.6±0.9 to 29.0±1.2 meq/100 g fat-free dry solids (P < 0.001). Renal papillary sodium content fell significantly from a control value of 234.6±8.0 to 182.46±10.0 meq/kg H20 after 2 wk of potassium restriction.Maximal urinary osmolality measured after 12 h of dehydration and 1.25 U pitressin IM was significantly decreased in rabbits after 2 wk of potassium restriction in both the adlibitum and controlled water intake groups (P < 0.001). The relationship between plasma potassium concentration and maximum urinary osmolality was significantly correlated in both the ad-libitum and controlled water intake groups, r = 0.73 and 0.68 (P < 0.001), respectively. In addition, refeeding KD rabbits with normal chow for 1 wk resulted in normalization of both plasma potassium levels and urinary concentrating ability.CCI`from control and KD rabbits were perfused in vitro at 250C. The hydraulic conductivity coefficient, Lp, was significantly reduced at all doses of ADH tested in tubules from KD rabbits when compared with control tubules. In addition, the maximal hydraulic conductivity in tubules from KD rabbits when tested with 200 uU/ml ADH at 37.50C was only 23% of control values (P < 0.05). Furthermore formed to evaluate the contribution of phosphodiesterase (PDIE) activity by using the potent PDIE inhibitor isobutylmethylxanthine (10-4 and 10-3 M) in the presence of ADH (200 U/ml).Although Lp was increased by PDIE inhibition in CCT from both control and KD animals, the overall hydroosmotic response in CCT from KD rabbits was still significantly reduced when compared with controls. The final experiments used forskolin to evaluate further the adenylate cyclase complex. The resulting hydroosmotic response in CCT from KD rabbits was almost identical to that obtained in controls. In conclusion, these data suggest that the decreased responsiveness of CCT from KD rabbits to ADH involves a step at or proximal to the stimulation of the catalytic subunit of adenylate cyclase, and that PDIE activity makes no contribution to this abnormal hydroosmotic response.

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“…The reduction in fluid delivery to late distal tubules suggests that during thiazide treatment less water is reabsorbed in the collecting ducts. This may result from a reduced sensitivity of the collecting ducts to vasopressin, possibly associated with the hypokalaemia of thiazide treatment (Beck & Webster, 1976 A paradoxical result with frusemide on sodium movements in human red blood cells BY S. C. BRAND and R. WHITTAM. Department of Physiology, The University, Leicester LEJ 7RH…”

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...

show abstract

Impaired urinary concentrating ability and cyclic AMP in K+-depleted rat kidney

Cited by 35 publications

References 1 publication

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex.

In vivo and in vitro studies of urinary concentrating ability in potassium-depleted rabbits.

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

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