Heparin suppresses endothelin-1 peptide and mRNA expression in cultured endothelial cells of spontaneously hypertensive rats

Heparin given se consistently lowers blood pressure in spontaneously hypertensive rats (SHR). This study was designed to examine heparin's effect on vasoconstrictor endothelin-1 production in cultured aortic endothelial cells (EC). Aortic EC from SHR and normotensive Wistar Kyoto rats (WKY) were cultured and incubated with or without different concentrations of heparin. Heparin suppressed endothelin-1 release and endothelin-1 mRNA expression in a dose- and a time-dependent fashion in both WKY and SHR. The suppressive effects were more augmented in SHR than in WKY: SHR versus WKY - endothelin-1 level at 6 h = 8 ± 1.8 versus 14 ± 2.2 pg/10⁶ cells (P< 0.01) and mRNA expression - 85 versus 52% maximal inhibition by heparin, 10 U/mL (=70 μg/mL) (P< 0.01). When heparin was added with transcriptional inhibitor actinomycin D and incubated for 30 min, no further inhibition of endothelin-1 mRNA level measured after another 30 minutes was observed compared with the endothelin-1 mRNA level in cultured EC of SHR treated with just actinomycin D at 30 min. These results suggest that heparin regulates endogenous endothelin-1 production by cultured EC, probably at the transcriptional level, and that this effect is more marked in SHR than in WKY.