Insulin nonattenuation of vasoactive agent-induced responses in mesangial cells from spontaneously hypertensive rats.
We recently found that insulin attenuates intracellular calcium transients and cell contraction caused by vasoactive agents in cultured rat mesangial cells. Because altered glomerular function may be causally related to the evolution of hypertension, we examined in the present study 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. Intracellular calcium concentration ([Ca2+]i) was measured with Fura-2 method in suspended mesangial cells. Pretreatment of mesangial cells with 5 micrograms/ml insulin for 120 minutes did not affect basal [Ca2+]i in either WKY or SHR mesangial cells. However, insulin pretreatment significantly attenuated [Ca2+]i transients to vasoactive agents in WKY mesangial cells. In contrast, [Ca2+]i transients to these agents were not attenuated by insulin in SHR mesangial cells. Additionally, SHR mesangial cell contraction in response to angiotensin II (Ang II) was not altered by insulin, while WKY mesangial cell contraction to Ang II was, as in normal Wistar rats, significantly reduced by insulin. Since we previously showed the possibility that the attenuation of calcium signal by insulin is via insulin-like growth factor I (IGF-I) receptor, we also examined the effect of IGF-I. In contrast to WKY mesangial cells, IGF-I-induced attenuation of [Ca2+]i responses to platelet activating factor was absent in SHR mesangial cells. [125I]-IGF-I binding in SHR mesangial cells was not significantly different from that in WKY mesangial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Inishi
Y
Y
Department of Internal Medicine, University of Tokyo School of Medicine, Toho University School of Medicine, Japan.
Okuda
T
T
Arakawa
T
T
Yasuda
C
C
Ohara
M
M
Kurokawa
K
K
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D016232:Endothelins / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects; D008297:Male; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D016232:Endothelins; D007328:Insulin; D010972:Platelet Activating Factor; D000804:Angiotensin II; D002118:Calcium