Cellular signaling and proliferative action of AVP in mesangium of SHR: effect of low density lipoprotein.

The present study was undertaken to determine whether low density lipoprotein (LDL) modulates the cellular action of arginine vasopressin (AVP) in cultured glomerular mesangial cells of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). The AVP-induced cellular signal transduction, including inositol 1,4,5-trisphosphate (IP3) production, fura-2 intracellular calcium measurements and cellular alkalinization, was significantly greater in cells of SHR than those of WKY. This is based on an increase in AVP V1 receptor number in cells of the SHR. Also, the AVP activation of mitogen-activated protein (MAP) kinase and [3H]thymidine incorporation was significantly exaggerated in cells of SHR compared with those of WKY. LDL at a concentration of 10 micrograms/ml augmented the cellular signaling and proliferative action of AVP in cells of WKY, but not in those of SHR. Since [3H]AVP receptor binding was not affected by the LDL pretreatment, LDL modulates the signal transduction between a location distal to the AVP receptors and proximal from the production of IP3 and diacylglycerol. These results indicate that an increase in AVP receptor capacity has a profound effect on the AVP-induced cellular signaling and proliferation, and that LDL has a slight alteration on the action of AVP in glomerular mesangial cells of SHR.