The Effect of Indomethacin on Vasopressin-Induced Antidiuresis in Man

1981 ◽  
Vol 61 (4) ◽  
pp. 493-495 ◽  
Author(s):  
P. L. Padfield ◽  
R. J. Grekin
Keyword(s):  
Weight Gain ◽  
Healthy Volunteer ◽  
Creatinine Clearance ◽  
Serum Potassium ◽  
Free Water ◽  
Free Water Clearance ◽  
Renal Response ◽  
Prostaglandin Production ◽  
Endogenous Prostaglandins ◽  
Water Clearance

1. The effect of 3 days' treatment with indomethacin on the renal response to infused vasopressin was assessed in eight healthy volunteer subjects. 2. Indomethacin produced significant weight gain and an increase in serum potassium without a change in creatinine clearance. 3. Although indomethacin reduced maximum free water clearance in five subjects, the antidiuresis produced by an incremental infusion of physiological amounts of vasopressin was no different whether indomethacin had been taken or not. 4. Indomethacin, in the dose we have used, is known to reduce prostaglandin production and we therefore conclude that endogenous prostaglandins do not inhibit the effect of physiological amounts of vasopressin on water clearance, which makes it unlikely that prostaglandins are important in the day-to-day modulation of the response to vasopressin.

Potentiation of the natriuretic effect of clonidine following indomethacin in the rat

1991 ◽  
Vol 69 (8) ◽  
pp. 1196-1203 ◽  
Author(s):  
Dorothea E. Blandford ◽  
Donald D. Smyth
Keyword(s):  
Sodium Excretion ◽  
Infusion Rate ◽  
Urine Volume ◽  
Free Water ◽  
Vehicle Group ◽  
Prostaglandin E ◽  
Free Water Clearance ◽  
Prostaglandin Production ◽  
Natriuretic Effect ◽  
Water Clearance

Previous studies have demonstrated a diuretic effect of clonidine at low intrarenal infusion rates with a natriuretic effect being observed at high infusion rates (≥3 μg∙kg−1∙min−1). The natriuresis at high infusion rates may have been secondary to increased renal prostaglandin production. We therefore evaluated the effects of indomethacin (a cyclooxygenase inhibitor) on the response to cionidine in the anesthetized rat. Intrarenal infusions of saline (vehicle) or clonidine (0.1, 0.3, 1, and 3 μg∙kg−1∙min−1) were examined both in the presence and absence of pretreatment with indomethacin (5 mg/kg, i.p.). Clonidine produced a dose-related increase in urine volume and free water clearance at 0.3, 1, and 3 μg∙kg−1∙min−1 as compared with the vehicle group. Sodium excretion and osmolar excretion were increased only at the highest infusion rate investigated. Following indomethacin pretreatment, clonidine produced a greater increase in urine volume at each infusion rate investigated. The indomethacin pretreatment also resulted in a potentiation of the natriuretic effect of clonidine at all infusion rates. Interestingly, this was associated with an increase in osmolar clearance but not free water clearance. These effects of indomethacin were reversed by infusion of prostaglandin E2. An infusion of prostaglandin E2 attenuated the indomethacin-induced increase in both urine flow rate and sodium excretion, indicating that the effects of indomethacin were mediated by prostaglandin inhibition. These results suggest that endogenous prostaglandin production attenuates the renal effects of clonidine, and as well, that in the presence of α2-adrenoceptor stimulation, prostaglandin E2 mediates an antidiuretic and antinatriuretic effect.Key words: clonidine, indomethacin, prostaglandin E2, diuresis, natriuresis.

Aldosterone increases urine production and decreases apical AQP2 expression in rats with diabetes insipidus

2006 ◽  
Vol 290 (2) ◽  
pp. F438-F449 ◽  
Author(s):  
Jakob Nielsen ◽  
Tae-Hwan Kwon ◽  
Jeppe Praetorius ◽  
Jørgen Frøkiær ◽  
Mark A. Knepper ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Diabetes Insipidus ◽  
Free Water ◽  
Sodium Balance ◽  
Apical Plasma Membrane ◽  
Sodium Reabsorption ◽  
Outer Medulla ◽  
Free Water Clearance ◽  
Urine Production ◽  
Water Clearance

Vasopressin and aldosterone are essential hormones in the regulation of water and sodium balance. Aldosterone regulates sodium reabsorption, although synergistic effects on collecting duct water permeability have been shown. We investigated the effects of 7-day aldosterone infusion or oral spironolactone treatment on water balance and aquaporin (AQP) 2 expression in rats with 21 days of lithium-induced nephrogenic diabetes insipidus (Li-NDI). In rats with Li-NDI, aldosterone markedly increased (271 ± 14 ml/24 h), whereas spironolactone decreased (74 ± 11 ml/24 h) urine production compared with rats treated with lithium only (120 ± 11 ml/24 h). Aldosterone increased free-water clearance and creatinine clearance, whereas spironolactone caused a decreased creatinine clearance but unchanged free-water clearance. Immunoblotting showed unchanged AQP2 expression in cortex/outer stripe of the outer medulla and inner medulla. In the inner stripe of the outer medulla aldosterone caused a decreased AQP2 expression, whereas spironolactone caused an increase compared with rats treated with lithium only. Semiquantitative confocal immunofluorescence microscopy of AQP2 immunolabeling showed reduced AQP2 expression in the apical plasma membrane domain in connecting tubule (CNT) and initial cortical collecting ducts (iCCD) in response to aldosterone-treated rats compared with rats treated with lithium only. Spironolactone significantly increased apical AQP2 expression in the iCCD compared with rats treated with lithium only. We also tested whether similar changes could be observed in vasopressin-deficient BB rats and found similar changes in urine production and subcellular AQP2 expression in the CNT and iCCD in response to aldosterone and spironolactone. This study shows that aldosterone treatment perturbs diabetes insipidus and is associated with AQP2 redistribution in CNT and iCCD likely mediated by the spironolactone-sensitive mineralocorticoid receptor.

scholarly journals Total Body Response to Mechanical Ventilation of Healthy Lungs: an Experimental Study in Piglets

2010 ◽  
pp. 545-552
Author(s):  
J Kobr ◽  
J Fremuth ◽  
K Pizingerová ◽  
S Fikrlová ◽  
P Jehlička ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Creatinine Clearance ◽  
Tidal Volume ◽  
Free Water ◽  
Myocardial Performance ◽  
Free Water Clearance ◽  
Neurohumoral Regulation ◽  
Group A ◽  
Group B ◽  
Water Clearance

The objective of our study was to assess the influence of mechanical ventilation on healthy body organs. Fifteen piglets (aged 6 weeks, 19-27 kg) were anesthetized, instrumented, and divided into three groups: Group A – spontaneously breathing, group B – mechanically ventilated with tidal volume 6 ml/kg, and group C – ventilated with tidal volume 10 ml/kg for 12 hours. The parameters of lung, heart, liver and kidney functions neurohumoral regulation and systemic inflammatory reaction were recorded initially (time-1) and after 12 hours (time-12) of mechanical ventilation. At the onset of experiment (time-1) the levels of soluble adhesive molecules were higher (CAM; P<0.01), glomerular filtration index and free water clearance were lower (P<0.05) in both ventilated groups than in group A. Right ventricle myocardial performance index was higher (RIMP; P<0.05) in group C when compared with group A. Levels of CAM (P<0.05) and creatinine clearance (P<0.01) were higher, free water clearance was lower (P<0.05) in group C when compared to group B. At time-12 the RIMP (P<0.05) and levels of CAM were increased (P<0.01), creatinine clearance was decreased (P<0.05) in both ventilated groups compared to the same parameter at time-1. Ventilation index was higher (P<0.05), and hypoxemic index was lower (P<0.01) in group C when compared to group B. In conclusion, this study showed that mechanical ventilation induced changes compatible with early inflammatory response in healthy animals. Higher tidal volumes had detrimental effect on ventilatory parameters, reduced myocardial performance and potentiated adverse reaction of other organs.

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