Funktion der Cyclooxygenaseisoformen an einem Tiermodell des Hyperprostaglandin-E2-Syndroms/antenatale Barttersyndroms

Patients with hyperprostaglandin-E2-syndrome/antenatal Bartter syndrome typically have renal salt and water wasting, hyper-reninism, hypercalciuria and juxtaglomerula hypertrophy. Antenatally, these patients have fetal polyuria, leading to polyhydramnions (10 l) and premature birth (28-34 pregnancy weeks). Most intriguing aspect of the syndrome is the association with a massively increased renal prostaglandin production which contributes substantially to the clinical picture, such as thirst, fever and growth-inhibition of the patients. With the experiments on a mouse-model should be shown which isoforms of cyclooxygenase COX1 and COX2 are most important to the production of PGE2 and the change of other parameters as renin-release, diurese and electrolyte-release. To solve these questions two different ways were chosen: first the genetically way in which the knock-out-mice are taken for COX1-/- and COX2-/- and second the pharmacological way in which different selective COX1 and COX2 inhibitors (Parecoxib, Rofecoxib, SC236, SC560) were used. Chronic use of loop diuretics, such as Furosemid, causes HPS/aBS-like symptoms. These experiments showed that COX2 is more important to clinically and pharmacologically symptoms. This statement has been published in other essays. But also SC560 showed an effect by decreasing thePGE2-production and diurese. This effect was not shown in any other essays before. Furthermore it could be said that not all results can be describe with classical COX1 and COX2-models. It is very likely that other isoforms are existing apart from COX1 and COX2 in the kidney, which are also important of physically functions and were not found out till yet. At the end could be said rofecoxib and Parecoxib always changed the parameter and the effect of furosemid was suppressed. It also could be said that SC236 and SC560 had a stronger effect. The question how PGE2 aggravate in salt and water regulation and which prostanoid receptors are involved is still unsolved. Further studies are necessary to explain the context.