INSULIN NONATTENUATION OF VASOACTIVE AGENT-INDUCED RESPONSES IN MESANGIAL CELLS FROM SPONTANEOUSLY HYPERTENSIVE RATS

We recently found that insulin attenuates intracellular calcium transi ents and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally r elated to the evolution of hypertension, we examined in the present st udy the effects of insulin on the functions of mesangial cells derived from spontaneously hypertensive rats (SHR) of 4- and 8-weeks of age. Age-matched Wistar Kyoto rats (WKY) were used as controls. Intracellul ar calcium concentration ([Ca2+](i)) was measured with Fura-2 method i n suspended mesangial cells. Pretreatment of mesangial cells with 5 mu g/ml insulin for 120 minutes did not affect basal [Ca2+](i) in either WKY or SHR mesangial cells. However, insulin pretreatment significant ly attenuated [Ca2+](i) transients to vasoactive agents in WKY mesangi al cells. In contrast, [Ca2+](i) transients to these agents were not a ttenuated by insulin in SHR mesangial cells. Additionally, SHR mesangi al cell contraction in response to angiotensin II (Ang II) was not alt ered by insulin, while WKY mesangial cell contraction to Ang II was, a s in normal Wistar rats, significantly reduced by insulin. Since we pr eviously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we a lso examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+](i) responses to platelet activatin g factor was absent in SHR mesangial cells. [I-125]-IGF-I binding in S HR mesangial cells was not significantly different from that in WKY me sangial cells. These data clearly show that the attenuation of mesangi al cell [Ca2+](i) responses and cell contraction by insulin, probably via IGF-I receptor, is absent in SHR mesangial cells, which may render SHR mesangial cells more sensitive to vasoactive agents.