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  • Title: Insulin-induced Ca2+ transport is altered in vascular smooth muscle cells of spontaneously hypertensive rats.
    Author: Touyz RM, Schiffrin EL.
    Journal: Hypertension; 1994 Jun; 23(6 Pt 2):931-5. PubMed ID: 8206630.
    Abstract:
    Intracellular calcium may be a mediator of insulin action in vascular smooth muscle cells. This study investigates effects of physiological concentrations of insulin on intracellular free calcium concentrations in primary unpassaged vascular smooth muscle cells derived from 3- and 17-week-old normotensive rats (Wistar and Wistar-Kyoto) and spontaneously, hypertensive rats (SHR). Underlying mechanisms responsible for insulin-evoked calcium responses were also studied. Basal calcium was significantly higher in 17-week SHR cells (134 +/- 8 nmol/L) compared with cells from Wistar-Kyoto (98 +/- 12 nmol/L) and Wistar (99 +/- 10 nmol/L) rats. Insulin (70 microU/mL) significantly increased calcium in all cells. Responses from 3-week rat cells were similar. The increase was amplified in 17-week SHR cells (177 +/- 7 nmol/L) compared with Wistar-Kyoto (130 +/- 14 nmol/L) and Wistar (132 +/- 16 nmol/L) cells. Genistein (0.1 mumol/L) and tyrphostin 23 (0.1 mumol/L) (tyrosine kinase inhibitors) completely abolished insulin-induced calcium effects. Stimulatory effects of insulin were significantly inhibited by 0.1 mumol/L diltiazem, staurosporine, calphostin C, and thapsigargin. The inhibitory effects of diltiazem (calcium channel antagonist) and the protein kinase C inhibitors staurosporine and calphostin C were significantly lower in cells from hypertensive compared with those from normotensive rats. Calcium recovery after insulin administration was delayed in SHR cells. In conclusion, insulin increases vascular smooth muscle cell calcium concentrations, possibly via calcium channel activation, protein kinase C-mediated mechanisms, and intracellular calcium mobilization. Alterations of these pathways as well as impaired calcium recovery to baseline may be associated with increased insulin-sensitive calcium responses in cells from SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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