COX-2 activity transiently contributes to increased water and NaCl excretion in the polyuric phase after release of ureteral obstruction.
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Release of bilateral ureteral obstruction (BUO) is associated with reduced expression of renal aquaporins (AQPs), polyuria, and impairment of urine-concentrating capacity. Recently, we demonstrated that 24 h of BUO is associated with increased cyclooxygenase (COX)-2 expression in the inner medulla (IM) and that selective COX-2 inhibition prevents downregulation of AQP2. In the present study, we tested the hypothesis that COX-2 activity increases in the postobstructive phase and that this increase in COX-2 activity contributes to polyuria and impaired urine-concentrating capacity. We examined the effect of the selective COX-2 inhibitor parecoxib (5 mg.kg(-1).day(-1) via osmotic minipumps) on renal functions and protein abundance of AQP2, AQP3, Na-K-2Cl cotransporter type 2 (NKCC2), and Na-K-ATPase 3 days after release of BUO. At 3 days after release of BUO, rats exhibited polyuria, dehydration and urine and IM tissue osmolality were decreased. There were inverse changes of COX-1 and COX-2 in the IM: COX-2 mRNA, protein, and activity increased, while COX-1 mRNA and protein decreased. Parecoxib reduced urine output 1 day after release of BUO, but sodium excretion and glomerular filtration rate were unchanged. Parecoxib normalized urinary PGE(2) and PGI(2) excretion and attenuated downregulation of AQP2 and AQP3, while phosphorylated AQP2 and NKCC2 remained suppressed. Parecoxib did not improve urine-concentrating capacity in response to 24 h of water deprivation. We conclude that decreased NKCC2 and collapse of the IM osmotic gradient, together with suppressed phosphorylated AQP2, are likely causes for the impaired urine-concentrating capacity and that COX-2 activity is not likely to mediate these changes in the chronic postobstructive phase after ureteral obstruction. (+info)
Phenotypes developed in secretin receptor-null mice indicated a role for secretin in regulating renal water reabsorption.
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Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp). Studies using Vp-deficient Brattleboro rats, however, indicated the existence of substantial Vp-independent mechanisms for membrane insertion, as well as transcriptional regulation, of this water channel. The Vp-independent mechanism(s) is clinically relevant to patients with X-linked nephrogenic diabetes insipidus (NDI) by therapeutically bypassing the dysfunctional Vp receptor. On the basis of studies with secretin receptor-null (SCTR(-/-)) mice, we report here for the first time that mutation of the SCTR gene could lead to mild polydipsia and polyuria. Additionally, SCTR(-/-) mice were shown to have reduced renal expression of AQP2 and AQP4, as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption process in these animals. By using SCTR(-/-) mice as controls and comparing them with wild-type animals, we performed both in vivo and in vitro studies that demonstrated a role for secretin in stimulating (i) AQP2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules and (ii) expression of this water channel under hyperosmotic conditions. The present study therefore provides information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating NDI patients. (+info)
Moxibustion, an alternative therapy, ameliorated disturbed circadian rhythm of plasma arginine vasopressin and urine output in multiple system atrophy.
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Previously no alternative therapy approach has been made to ameliorate disturbed circadian arginine vasopressin rhythm (C-AVP-R) in multiple system atrophy (MSA). A 65-year-old man with MSA showed loss of C-AVP-R and nocturnal polyuria. We performed moxibustion at specific acupuncture points on the bladder and inside the feet, once a day, 3 times a week, for 6 months. After the treatment, his C-AVP-R appeared to be normal, and the nocturnal urine output decreased to 75% (p<0.01). Together with the previous studies, it seems possible that somatic warm stimulation by moxibustion in specific points might have facilitated AVP secretion in this patient. (+info)
Masking of central diabetes insipidus and hypogonadotrophic hypogonadism by germ cell tumour in suprasellar--pineal region.
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A patient with beta hCG-secreting germ cell carcinoma of the pineal and suprasellar regions presented with hydrocephalus, Parinaud's syndrome, hypopituitarism and polyuria. Central diabetes insipidus was strongly suspected although the water deprivation test was not diagnostic. The polyuria however, responded to ADH analogue when the hypothyroidism and hypocortisolism were treated. Pubertal development was evident and serum testosterone was normal despite the low FSH/LH, suggesting hCG stimulation of Leydig cells. This case illustrates that a beta hCG-germ cell tumour of the suprasellar region causing hypopituitarism can mask the presence of central diabetes insipidus and hypogonadotrophic hypogonadism. (+info)
Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition.
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Acute physiological hyperinsulinemia increases skeletal muscle capillary blood volume (CBV), presumably to augment glucose and insulin delivery. We hypothesized that insulin-mediated changes in CBV are impaired in type 2 diabetes mellitus (DM) and are improved by angiotensin-converting enzyme inhibition (ACE-I). Zucker obese diabetic rats (ZDF, n = 18) and control rats (n = 9) were studied at 20 wk of age. One-half of the ZDF rats were treated with quinapril (ZDF-Q) for 15 wk prior to study. CBV and capillary flow in hindlimb skeletal muscle were measured by contrast-enhanced ultrasound (CEU) at baseline and at 30 and 120 min after initiation of a euglycemic hyperinsulinemic clamp (3 mU.min(-1).kg(-1)). At baseline, ZDF and ZDF-Q rats were hyperglycemic and hyperinsulinemic vs. controls. Glucose utilization in ZDF rats was 60-70% lower (P < 0.05) than in controls after 30 and 120 min of hyperinsulinemia. In ZDF-Q rats, glucose utilization was impaired at 30 min but similar to controls at 120 min. Basal CBV was lower in ZDF and ZDF-Q rats compared with controls (13 +/- 4, 7 +/- 3, and 9 +/- 2 U, respectively). With hyperinsulinemia, CBV increased by about twofold in control animals at 30 and 120 min, did not change in ZDF animals, and increased in ZDF-Q animals only at 120 min to a level similar to controls. Anatomic capillary density on immunohistology was not different between groups. We conclude that insulin-mediated capillary recruitment in skeletal muscle, which participates in glucose utilization, is impaired in animals with DM and can be partially reversed by chronic ACE-I therapy. (+info)
Multiple renal cysts, urinary concentration defects, and pulmonary emphysematous changes in mice lacking TAZ.
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Cyclical edema in a patient with hypothalamic disorders and chronic glomerulonephritis: arginine vasopressin-dependent atrial natriuretic hormone release.
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A 28-year-old woman had hypothalamic disorders (amenorrhea, obesity, psychiatric abnormalities, polydipsia and fever) and chronic glomerulonephritis. She also suffered from general edema associated with cyclical oliguria and polyuria. Her body weight and plasma osmolality increased during the oliguria phase lasting 2 to 8 days and decreased after paroxysmal polyuria accompanied by the natriuresis. These episodes occurred repeatedly, regardless of the treatment with or without diuretics. The release of arginine vasopressin in response to increased plasma osmolality was exaggerated, but changes in plasma volume did not affect arginine vasopressin release. Plasma atrial natriuretic hormone increased in response to a rise in plasma arginine vasopressin and plasma volume during the oliguria phase, thereby resulting in the diuresis and natriuresis. The renin-angiotensin-aldosterone system was secondarily activated by body fluid depletion and diuretics, and this might play an additive role in general swelling. Plasma gonadal hormones did not change to explain the edema. The mechanism of this cyclical edema remains unknown, but it is likely that hypothalamic dysfunction related to psychiatric abnormalities may exaggerate arginine vasopressin release, and enhanced renal sympathetic activity may cause retention of Na and water, and the increase in atrial natriuretic hormone release responding to the plasma volume expansion may bring about the diuresis and natriuresis. (+info)