The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 ± 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI2), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 ± 0.15 to 1.8 ± 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 ± 0.2 to 1.8 ± 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 ± 0.12 vs. 3.15 ± 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI2 analogue, iloprost, can induce U-AQP2 excretion independent of AVP.

1.
Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S: Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 1993;361:549–552.
2.
Sasaki S, Fushimi K, Saito H: Cloning characterization and chromosomal mapping of human aquaporin of collecting duct. J Clin Invest 1994;93:1250–1256.
3.
Nielsen S, Di Giovanni SR, Christensen EI, Knepper MA, Harris HW: Cellular and subcellular immunolocalization of vasopressin-regulated water channel in rat kidney. Proc Natl Acad Sci USA 1992;90:11663–11667.
4.
Marples D, Knepper MA, Nielsen S: Captopril increases aquaporin-2 water channel expression despite causing polyuria in rats. J Am Soc Nephrol 1998;9:23A.
5.
Marples D, Knepper MA, Nielsen S: Inhibition of prostaglandins abolishes thirsting-induced AQP2 expression in collecting duct. J Am Soc Nephrol 1998;9:22A.
6.
Sakairi Y, Jacobson HR, Noland TD, Breyer MD: Luminal prostaglandin E receptors regulate salt and water transport in rabbit collecting duct. Am J Physiol 1995;38:F257–F265.
7.
Orloff J, Handler JS, Bergstrom S: Effect of prostaglandin (PGE1) on the permeability response of toad bladder to vasopressin. Theophylline and adenosine 3′,5′ monophosphate. Nature 1965;205:397.
8.
Hebert RL, Regnier L, Peterson LN: Rabbit cortical collecting ducts express a novel prostaglandin receptor. Am J Physiol 1995;268:F145–F154.
9.
Menè P, Dunn MJ: Vascular, glomerular and tubular effects of angiotensin II, kinins and prostaglandins; in Seldin DW, Giebisch G (eds): The Kidney, Physiology and Pathophysiology, ed 2. New York, Raven Press, 1992, pp 1205–1248.
10.
Coleman RA, Kennedy I, Humprey PP, Bunce K, Lumley PA: Prostanoids and their receptors; in Hansch C (ed): Comprehensive Medicinal Chemistry. Oxford, Pergamon, 1989, pp 643–714.
11.
Angeli P, Gatta A, Caregaro L, Menon F, Sacerdoti D et al: Effects of iloprost, a prostacyclin analog derivative, on renal plasma flow, renal function and renin aldosterone system in humans. Clin Pharmacol Ther 1988;44:211–216.
12.
Kanno K, Sasaki S, Hirata Y: Urinary excretion of aquaporin-2 in patients with diabetes insipidus. N Engl J Med 1995;332:1540–1545.
13.
Ohara M, Martin YP, Xu D, St John J, et al: Upregulation of aquaporin-2 water channel expression in pregnant rats. J Clin Invest 1998;101:1076–1083.
14.
Patil RV, Han Z, Way MB: Regulation of water channel activity of aquaporin 1 by arginine vasopressin and atrial natriuretic peptide. Biochem Biophys Res Commun 1997;238:392–396.
15.
Schlondorff D: Renal prostaglandin synthesis: Sites of production and specific action of prostaglandins. Am J Med 1986;81(suppl 2B):1–11.
16.
Griglewsky RJ, Stork G: PGI2 and its stable analogue iloprost; in Griglewsky RJ, Stork G (eds): Prostaglandins. Berlin, Springer, 1987.
17.
Baumgarten R, Van de Pol MHJ, Deen PMT, Van Os CH, Wetzels JFM: Dissociation between urinary excretion of aquaporin 2 and vasopressin action in healthy volunteers. J Am Soc Nephrol 1998;9:15A.
18.
Grenier FC, Allen ML, Smith WL: Interrelationships among prostaglandins, vasopressin and cAMP in renal papillary collecting tubule cells in culture. Prostaglandins 1982;24:547–565.
19.
Veis JH, Dillingham MA, Beri T: Effects of prostacyclin on the cAMP system in cultured rat inner medullary collecting duct cells. Am J Physiol 1990;258:F1218–F1223.
20.
Villa E, Garcia-Robles R, Haas J, Romero JC: Comparative effect of PGE2 and PGI2 on renal function. Hypertension 1997;30:664–666.
21.
Ylitalo P, Kaukinen S, Nurmi AK, Seppala E, Pessi T, Vapaatalo H: Effects of a prostacyclin analog iloprost on kidney function, renin-angiotensin and kallikrein-kinin systems, prostanoid and catecholamines in man. Prostaglandins 1985;29:1063–1071.
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