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Aim: This study investigates key components of the renin-angiotensin system (RAS) which play a central role in nephrogenesis and possibly in fetal programming of arterial hypertension in adult life. Methods: We compared a genetic rat model with inborn nephron deficit, the Munich Wistar Fromter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postnatal day 7 (D7). Results: At E19 renal mRNA of angiotensin II type 1a (AT1a) (-50%, P<0.05) and type 1b {ATlb) (-55%, P<0.05) receptors were significantly decreased and renal mRNA expression of angiotensin II type 2 (AT2) receptor was fivefold increased in MWF (n=8) as compared to Wistar rats (n=8). At D7 renal mRNA expression of AT1a (-42%, P<0.05) remained lower in MWF (n=8) as compared to Wistar (n=7). Renal mRNA expression ofAT2 (-30%, P>0.05) decreased in MWF (n=8) to about the level of the Wistar control (n=6). Conclusions: Altered fetal expression of key molecules of the renin-angiotensin system in MWF indicates a possible role in genetic low nephron number hypertension. [ABSTRACT FROM AUTHOR]

Aims: The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life. Methods: We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7). Results: Renal OPN mRNA (-75%, P<0.05) and protein expression (-38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05). Conclusions: Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease. [ABSTRACT FROM AUTHOR]