deamino-arginine-vasopressin and Hyperaldosteronism

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076-F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207-217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-D-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-beta-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, alpha- and gamma-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and gamma-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, alpha- or gamma-ENaC or increased MAP associated with "escape."

Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 2; Adrenalectomy; Aldosterone; Animals; Blood Pressure; Corticosterone; Deamino Arginine Vasopressin; Diuresis; Drinking; Epithelial Sodium Channels; Gene Expression Regulation; Glomerular Filtration Rate; Hyperaldosteronism; Hypertension; Kidney Tubules, Collecting; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Sodium Channels; Sodium Chloride Symporters; Vasopressins

1. Urinary PGE is elevated above normal in patients with Bartter's syndrome, central and nephrogenic diabetes insipidus. 2. K+ loading, Mg2+ infusion, and water-loading-all of which increased urine volume-were associated with augmented urinary PGE in Bartter's syndrome, while fluid restriction decreased urinary PGE to normal. 3. Antidiuresis in central diabetes insipidus with DDAVP, and with indomethacin or ibuprofen in nephrogenic diabetes insipidus, is associated with a decrease in urinary PGE. 4. High urine volume may be a contributing factor to the elevated urinary PGE in Bartter's syndrome, central and nephrogenic diabetes insipidus.

Topics: Bartter Syndrome; Deamino Arginine Vasopressin; Diabetes Insipidus; Humans; Hyperaldosteronism; Kidney; Magnesium; Male; Potassium; Prostaglandins E; Urine

We have investigated the effect of indomethacin and DDAVP on water excretion in a patient with familial Bartter's syndrome in whom urinary concentration was impaired during ad libitum fluid intake without any decrease in maximal concentrating ability. In response to indomethacin urine osmolality and free water reabsorption increased, simultaneously with the decrease in the excretion of prostaglandin E2. The indomethacin induced improvement was however less than that obtained after DDAVP with or without indomethacin. The results can be interpreted on the basis of either a direct "vasopressin-like" action of indomethacin or abolishment of the peripheral vasopressin--prostaglandin interaction. The clinical implication is that the theoretical possibility of indomethacin-induced inappropriate ADH syndrome should be borne in mind when a patient is treated with this drug on a long term basis.

Topics: Adult; Bartter Syndrome; Deamino Arginine Vasopressin; Diuresis; Humans; Hyperaldosteronism; Indomethacin; Kidney; Male; Osmolar Concentration; Prostaglandins; Vasopressins; Water Deprivation