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Protective role of a novel erythrocyte-derived depressing factor on blood vessels of renovascular hypertensive rats.

Authors: Pang, H  Wen, YY  Ma, N  Wang, YT  Shi, L 
Citation: Pang H, etal., Clin Exp Pharmacol Physiol. 2007 May-Jun;34(5-6):393-8.
Pubmed: (View Article at PubMed) PMID:17439406
DOI: Full-text: DOI:10.1111/j.1440-1681.2007.04561.x

1. We have isolated a novel human erythrocyte-derived depressing factor (EDDF) that has a significant antihypertensive effect in various rat models of hypertension. The aim of the present study was to examine the mechanisms of action of EDDF on vascular function in two-kidney, one-clip (2K1C) renovascular hypertensive rats. 2. The EDDF was prepared from human erythrocytes. Experiments were performed in 18 male Wistar rats. The vascular ring perfusion assay and a two-photon laser scanning fluorescence microscope (TMP) were used to evaluate the vascular contractile response. The effects of EDDF on phenylephrine (PE)- and noradrenaline (NA)-induced vascular contraction were evaluated in 2K1C hypertensive rats. The proliferation and DNA synthesis in vascular smooth muscle cells (VSMC) were determined using the [3H]-TdR (thymidine) incorporation and 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assays. Flow cytometry, reverse transcription-polymerase chain reaction and western blots were used to measure cell cycle and apoptotic profiles, platelet-derived growth factor (PDGF)-A expression and the activity of extracellular signal-regulated kinase (ERK)-1/2, as well as the expression of cyclin D1 and cyclin-dependent kinase (CDK) 4. 3. At 10(-5) g/mL, EDDF significantly decreased the PE- and NA-induced hypertensive vascular contraction. In addition, EDDF inhibited DNA synthesis in primary VSMC from 2K1C rats. The mRNA expression of PDGF-A in VSMC was twofold higher in 2K1C rats compared with control rats, whereas EDDF significantly inhibited the increment in PDGF-A mRNA expression. In addition, EDDF inhibited the phosphorylation of ERK1/2 and decreased the expression of cyclin D1 and CDK4; p21 (Cip1) levels were increased after treatment with EDDF. 4. In conclusion, EDDF inhibits VSMC proliferation in 2K1C rats through G0/G1 cell cycle arrest. The effects may be mediated, in part, by enhanced expression of p21 (Cip1) and the inhibition of ERK1/2 phosphorylation and the expression of cyclin D1/CDK4 and PDGF-A.


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RGD Object Information
RGD ID: 2289672
Created: 2008-02-05
Species: All species
Last Modified: 2008-02-05
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.