Aim: The study was undertaken to determine whether ageing affects kidney expression of the aquaporin-2 (AQP2) water channel in glucocorticoid-deficient rats.
Methods: After adrenalectomy, 6- and 52-week-old Sprague–Dawley rats received aldosterone via osmotic minipumps (glucocorticoid-deficient rats). Aldosterone and dexamethasone were administered to control rats of the same age.
Results: An acute water load test verified impairment of water excretion in both young and aged rats with glucocorticoid deficiency, with a more serious impairment in the older rats. Despite the presence of hypoosmolality, non-suppressible release of arginine vasopressin (AVP) was particularly evident in the aged rats with glucocorticoid deficiency in comparison with the young rats. The expression levels of AQP2 mRNA and protein were lower in the aged rats, with a particularly large reduction in AQP2 protein expression. AQP2 expression levels were significantly augmented in the glucocorticoid-deficient rats compared with the controls under both basal and water-loaded conditions. Acute water loading did not suppress expression of AQP2 mRNA and protein, and the percentage increases in AQP2 mRNA and protein expression vs. the respective controls were more pronounced in the 52-week-old glucocorticoid-deficient rats compared with the 6-week-old rats.
Conclusion: The findings indicate that upregulation of AQP2 expression is maintained dependent upon non-suppressible release of AVP in rats with glucocorticoid deficiency, and that AQP2 plays a crucial role in persistent impairment of water excretion in aged rats with glucocorticoid deficiency.
[Show abstract][Hide abstract] ABSTRACT: We tested whether severe congestive heart failure (CHF), a condition associated with excess free-water retention, is accompanied by altered regulation of the vasopressin-regulated water channel, aquaporin-2 (AQP2), in the renal collecting duct. CHF was induced by left coronary artery ligation. Compared with sham-operated animals, rats with CHF had severe heart failure with elevated left ventricular end-diastolic pressures (LVEDP): 26.9 ± 3.4 vs. 4.1 ± 0.3 mmHg, and reduced plasma sodium concentrations (142.2 ± 1.6 vs. 149.1 ± 1.1 mEq/liter). Quantitative immunoblotting of total kidney membrane fractions revealed a significant increase in AQP2 expression in animals with CHF (267 ± 53%, n = 12) relative to sham-operated controls (100 ± 13%, n = 14). In contrast, immunoblotting demonstrated a lack of an increase in expression of AQP1 and AQP3 water channel expression, indicating that the effect on AQP2 was selective. Furthermore, postinfarction animals without LVEDP elevation or plasma Na reduction showed no increase in AQP2 expression (121 ± 28% of sham levels, n = 6). Immunocytochemistry and immunoelectron microscopy demonstrated very abundant labeling of the apical plasma membrane and relatively little labeling of intracellular vesicles in collecting duct cells from rats with severe CHF, consistent with enhanced trafficking of AQP2 to the apical plasma membrane. The selective increase in AQP2 expression and enhanced plasma membrane targeting provide an explanation for the development of water retention and hyponatremia in severe CHF.
Proceedings of the National Academy of Sciences 05/1997; 94(10):5450-5455. DOI:10.1073/pnas.94.10.5450 · 9.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies revealed that chronic (days) vasopressin treatment stimulates amiloride-sensitive sodium transport in isolated renal cortical collecting ducts and increases the abundance of beta- and gamma-subunits of the epithelial sodium channel (ENaC) in the kidney. The aim of the present work was to investigate in vivo the cellular basis of these effects. The long-term effect of V2 vasopressin agonist (1-deamino-8-D-arginine vasopressin (dDAVP)) on the abundance and subcellular localization of ENaC along the rat renal collecting system was determined by immunohistochemistry and laser confocal microscopy. Moreover, we studied by real-time reverse transcriptase-polymerase chain reaction the effect of vasopressin on proteins implicated in the regulation of ENaC (Nedd4-2, prostasin, Sgk1). After 5 days of administration, dDAVP markedly increased the intracellular pool of the beta- and gamma-ENaC subunits in the principal cells, with an increasing gradient from connecting tubule to the outer medullary collecting duct, but did not increase any subunit at the cell surface. The apical immunostaining of ENaC increased in response to sodium restriction, as expected, but dDAVP did not further enhance this apical labelling. dDAVP increased the gene expression of prostasin in the cortex but not that of Nedd4-2 and Sgk1. These findings suggest that the previously reported increase in sodium transport induced by sustained stimulation of vasopressin V2 receptor is probably mediated by other mechanism than an increase in the apical density of ENaC.
Kidney International 04/2006; 69(6):1024-32. DOI:10.1038/sj.ki.5000211 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CRH and vasopressin (VP), the main regulators of pituitary ACTH secretion, co-exist in parvocellular cells of the PVN, but their levels of expression are regulated differentially during manipulations of the hypothalamic pituitary adrenal (HPA) axis. The effects of glucocorticoids on this system was studied using in situ hybridization with intronic and exonic probes to measure changes in CRH and VP messenger RNA (mRNA) and heteronuclear (hn) RNA in 48-h adrenalectomized (ADX) rats receiving injections of corticosterone (2.8 mg/100 g, ip) or vehicle. We also determined the time course of changes in VP expression following the first 72 h of ADX. Levels of VP heteronuclear (hn) RNA and the number of parvocellular cells containing VP hnRNA remained very low in sham operated rats, whereas biphasic changes were observed after ADX. Grain density levels increased 11.5-fold over sham-operated controls by 6 h, declined to 2-fold by 18 h, to increase again to 10- and 20-fold by 48 and 72 h, respectively. In 48-h ADX rats, vehicle injection increased CRH hnRNA levels transiently (11-fold the basal by 15 and 30 min), returning to basal at 60 min, whereas VP hnRNA levels increased progressively up to 28-fold the basal by 2 h. Corticosterone injection had no significant effect on vehicle-induced increases in CRH hnRNA, in spite of marked elevations in circulating corticosterone. In contrast to CRH, VP hnRNA levels increased only transiently by 15 min, and then decreased below basal (near sham-ADX levels) by 2 h. The data show that in normal conditions the responsiveness of parvocellular neurons to stress is under marked inhibition by the low resting levels of glucocorticoids, and that the sensitivity of CRH and VP transcription to glucocorticoid feedback is markedly different.
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