MESANGIAL CELL ABNORMALITIES IN SPONTANEOUSLY HYPERTENSIVE RATS BEFORE THE ONSET OF HYPERTENSION

To identify kidney biosynthetic abnormalities that may precede the ons et of hypertension, we studied the expression of fibronectin (FN) and collagen IV (Cell IV) in young SHR (14 weeks of age) whose systolic bl ood pressure was normal and similar to that of age matched control WKY rats. In isolated glomeruli the level of FN protein assessed by immun oblotting tended to be lower in the SHR than in the WKY rats. By North ern analysis the FN/actin mRNA ratio was significantly lower in glomer uli from SHR (0.56 +/- 0.47) than in glomeruli from WKY rats (2.0 +/- 0.8). These abnormalities were maintained in vitro since the expressio n of FN was significantly lower in SHR than in WXY cultured mesangial cells (FN/actin mRNA ratio = 0.84 +/- 0.46 vs. 1.9 +/- 0.7, P = 0.029) . No differences in Coil IV mRNA or protein levels were observed in SH R glomeruli and mesangial cells when compared with WKY rats. The level s of aortic FN and Coil IV mRNAs were not different in SHR and WKY rat s. In addition, mesangial cells from SHR showed a significantly higher growth rate than those from WKY. The biosynthetic and proliferative a bnormalities observed in the SHR mesangial cells appear to reflect gen etic characteristics, and could provide novel insights into cellular m echanisms linking the genetics of hypertension with predisposition to glomerular pathology.