Primate kidney function in hemorrhagic shock as influenced by dibutyryl cyclic AMP

1976 ◽  
Vol 230 (3) ◽  
pp. 724-730 ◽  
Author(s):  
EE Selkurt

Standardized hemorrhagic shock was employed to study alterations in electrolyte and water handling in the owl monkey, either normally hydrated or moderately dehydrated. Increase in fractional clearance of osmolarity,sodium, and calcium occurred with retransfusion after the hypotensive phase. In the hydrated animals, free-water clearance became positive, and the urine-to-plasma osmolarity ratio [(U/P)osM] decreased below 1.0. In the dehydrated animals, free-water reabsorption (TCH2O) decreased but remained negative,while (U/P)osM remained above 1.0. Dibutyryl cyclic AMP (DBcAMP) was infused into the renal arterial supply in an attempt to correct a possible deficiency of cyclic AMP production. In the hydrated group, free-water clearance (CH2O) became more positive with infusion, and (U/P)osM decreased even further, with no effect on fractional sodium clearance. Effects were less or absent in the dehydrated group. Possible explanations for the observed effects of DBcAMP are considered. It was concluded that the loss of concentrating power seen in hemorrhagic shock occurs at a step beyond the production of cyclic AMP by adenylate cyclase.

2010 ◽  
Vol 88 (12) ◽  
pp. 1191-1201 ◽  
Author(s):  
S. Mostafa Shid Moosavi ◽  
Masoud Haghani

The exact mechanism underlying thiazides-induced paradoxical antidiuresis in diabetes insipidus is still elusive, but it has been hypothesized that it is exerted either via Na+-depletion activating volume-homeostatic reflexes to decrease distal delivery, or direct stimulation of distal water reabsorption. This study examined how these two proposed mechanisms actually cooperate to induce an acute bendroflumethiazide (BFTZ)-antidiuretic effect in nephrogenic diabetes insipidus (NDI). Anaesthetized rats with lithium (Li)-induced NDI were prepared in order to measure their renal functional parameters, and in some of them, bilateral renal denervation (DNX) was induced. After a 30 min control clearance period, we infused either BFTZ into 2 groups, NDI+BFTZ and NDI/DNX+BFTZ, or its vehicle into a NDI+V group, and six 30 min experimental clearance periods were taken. During BFTZ infusion in the NDI+BFTZ group, transiently elevated Na+ excretion was associated with rapidly increased urinary osmolality and decreased free water clearance, but Li clearance and urine flow declined in the later periods. However, in the NDI/DNX+BFTZ group, there was persistently elevated Na+ excretion with unchanged Li clearance and urine flow during the experimental period, while alterations in free water clearance and urinary osmolality resembled those in the NDI+BFTZ group. In conclusion, BFTZ initially exerted two direct effects of natriuresis–diuresis and stimulating free water reabsorption at the distal nephron in NDI, which together elevated Na+ excretion and urinary osmolality but kept the urine volume unchanged in the first hour. Thereafter, the resultant sodium depletion led to the activation of neural reflexes that reduced distal fluid delivery to compensate for BFTZ-induced natriuresis–diuresis which, in cooperation with the direct distal BFTZ-antidiuretic effect, resulted in excretion of urine with a low volume, high osmolality, and normal sodium.


1995 ◽  
Vol 79 (6) ◽  
pp. 2069-2077 ◽  
Author(s):  
B. J. Freund ◽  
S. J. Montain ◽  
A. J. Young ◽  
M. N. Sawka ◽  
J. P. DeLuca ◽  
...  

Glycerol ingestion has been shown to mediate hyperhydration; however, the mechanism(s) responsible for this improved fluid retention is not well understood. This study examined the hormonal, renal, and vascular fluid responses to glycerol hyperhydration in 11 resting male volunteers who ingested one of two experimental solutions and then a water bolus. The volume of fluid ingested was determined from the subjects' measured total body water (TBW; total volume = 37 ml/l TBW, 1,765 +/- 162 ml). Experimental solutions (5.0 ml/l TBW) were matched for color and taste and differed only in that one contained 1.5 g glycerol/l TBW (total osmolar load = 777 +/- 24 mosmol). Nine of the 11 subjects also completed a control trial during which no fluid was ingested. Glycerol ingestion (GI) resulted in greater fluid retention than the ingestion of water alone (WI; 60 vs. 32% 3-h posthyperhydration, P < 0.01). This improved fluid retention with GI resulted from lower urine flow rates (peak 6.2 vs. 10.5 ml/min, P < 0.01) associated with lower free water clearance rates (peak = 1.2 vs. 8.2 ml/min, P < 0.01). Hyperhydration had no effect on plasma atrial natriuretic peptide concentrations. Changes in plasma aldosterone were unrelated to differences in fluid retention. Antidiuretic hormone concentrations (ADH) were significantly reduced from prehyperhydration levels during both hyperhydration trials but tended (P = 0.07) to rise during GI compared with WI at the very time urine flow and free water clearance differences were also evident. This suggests that ADH may, in part, be responsible for glycerol's effectiveness, although differences in ADH concentrations were small and near the assay's sensitivity limits. Alternatively, glycerol's effectiveness may result from its directly increasing the kidneys' medullary concentration gradient and, hence, water reabsorption.


2020 ◽  
Vol 49 (3) ◽  
pp. 439-445 ◽  
Author(s):  
Thomas F Monaghan ◽  
Donald L Bliwise ◽  
Marie-Astrid Denys ◽  
An-Sofie Goessaert ◽  
Veerle Decalf ◽  
...  

Abstract Background this study compares diuresis rate, sodium clearance and free water clearance (FWC) by age and time of day (nighttime vs. daytime) in subjects with and without nocturnal polyuria (NP) to determine whether these variables affect the phenotype of NP. Methods post hoc analysis of two prospective observational studies. Eight urine samples collected at 3-h intervals and a single blood sample were used to calculate daytime (10a/1p/4p/7p/10p) and nighttime (1a/4a/7a) diuresis rates, sodium clearance and FWC. Three mixed linear models were constructed for diuresis rate, sodium clearance and FWC using four predictor variables: NP status (present [nocturnal urine production &gt;90 ml/h] vs. absent [≤90 ml/h]), time of day, age and study identification. Results subjects with NP experienced higher nighttime versus daytime diuresis rates, sodium clearance and FWC. Regardless of NP status, increased age was accompanied by an increase in the ratio of nighttime/daytime diuresis rate, nighttime sodium clearance and daytime sodium clearance. FWC showed a complex age effect, which was independent of time of day or NP status. Conclusions age-related increases in nighttime/daytime diuresis rate, 24-h sodium clearance and 24-h FWC are not specific to subjects with NP. The age-related surge in either nocturnal sodium clearance or nocturnal FWC may represent the relevant substrate for behavioural or pharmacologic interventions targeting sodium diuresis or free water diuresis, respectively. Increases in FWC in older age groups may reflect impaired circadian rhythmicity of endogenous AVP or changes in responsiveness of the aged nephron to water clearance.


1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.


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