Lysophosphatidic acid (LPA) is a platelet-derived phospholipid which has been shown to cause immediate hypertension in rats. The following experiments were designed to assess the involvement of endothelin-1 (ET-1) in LPA-induced hypertension. LPA was found to upregulate preproET-1 transcripts in endothelial cells which were derived from rat hearts and aortae in a dose and time-dependent manner. PreproET-1 mRNA level was elevated within 15 min and maximal induction was achieved by 30 min after the addition of 0.5 μM LPA. Cycloheximide superinduced the preproET-1 mRNA level and actinomycin D abolished the induction. In addition, the induction could be blocked by H7, an inhibitor of protein kinase C. These findings indicate that the induction of preproET-1 transcripts by LPA involves the activation of protein kinase C and de novo RNA synthesis. Since ET-1 is a very potent vasoconstrictor with long lasting effect, the increase in ET-1 production may serve to amplify and augment the effect of LPA on hypertension.
Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-14741 |
Date | 01 December 1997 |
Creators | Chua, C. C., Chua, B. H.L., Hamdy, R. C. |
Publisher | Digital Commons @ East Tennessee State University |
Source Sets | East Tennessee State University |
Detected Language | English |
Type | text |
Source | ETSU Faculty Works |
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