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Acta Physiologica 2010; Volume 198, Supplement 677
Joint Meeting of the Scandinavian and German Physiological Societies
3/27/2010-3/30/2010
Copenhagen, Denmark
ACE-INHIBITION DURING NEPHROGENESIS OBSTRUCTS NEONATAL DISSIPATION OF INTERSTITIAL HYALURONAN. INVOLVEMENT OF HAS2 AND HYAL1.
Abstract number: O-TUE-3-2
STRIDH1 S, CHEN1 Y, RUGHEIMER1 L, ASTRAND1 ABM, JOHNSSON1 C, FRIBERG1 P, OLERUD1 J, PALM1 F, HANSELL1 P
Neonatal inhibition of the reninangiotensin system (RAS) in rats results in long-term abnormal renal morphology and function. Hyaluronan (HA), which is involved in morphogenesis and inflammation, is severely elevated in the adult rat kidney after neonatal RAS inhibition. To elucidate mechanisms, intrarenal HA content was followed neonatally, with and without ACE-inhibitor (ACEI, enalapril, days 313), together with the expression of hyaluronan synthases (HAS1-3) and hyaluronidases (Hyal1-4). In vehicle-treated 6-8 days old rats, cortical HA content was high (~100 mg·g-1 dry weight (dw)) after which the content rapidly decreased days 10-21, reaching adult low levels (7±2 mg·g-1 dw). Medullary HA content was high days 6-8 (~600 mg·g-1 dw), then gradually reduced to 12-fold above cortical levels at day 21 (85±10 mg·g-1 dw). In ACEI-treated rats, cortical HA remained high days 6-21 (90±26 mg·g-1 dw). The medullary reduction was attenuated and over 3-fold that in controls at day 21 (308±61 mg·g-1 dw). HAS2 mRNA expression corresponded temporally to the changes in HA. Control HAS2 decreased gradually after birth. In ACEI-treated animals, cortical HAS2 did not decrease past day 12, ending at twice the control expression. Medullary HAS2 followed the controls. Medullary Hyal1 expression decreased in ACEI-treated animals as opposed to controls. In conclusion, neonatal high renal HA content is rapidly reduced during completion of nephrogenesis in the rat. This reduction depends on angiotensin II tonus and involves reduced cortical HAS2 mRNA and increased medullary Hyal1 mRNA. Due to its proinflammatory and water-binding properties, HA accumulation after ACEI-treatment can partly explain the generation of the abnormalities, which during adulthood include tubulointerstitial inflammation and reduced urine concentrating ability.
To cite this abstract, please use the following information:
Acta Physiologica 2010; Volume 198, Supplement 677 :O-TUE-3-2