Abstract
BackgroundHyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction.MethodsThe effects of STA on vascular relaxation in rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) were measured by using Multi Myograph System. The levels of nitric oxide (NO), tetrahydrobiopterin (BH4) and guanosine 3′, 5′ cyclic monophosphate (cGMP) were determined. Endothelial nitric oxide synthase (eNOS) dimers and monomers were assayed by using Western blotting. GTP cyclohydrolase 1 (GTPCH1) and dihydrofolate reductase (DHFR) expressions were measured by using quantitative reverse transcriptase-PCR (qRT-PCR) and Western blotting.ResultsSTA effectively blocked Hcy-induced impairment of endothelium-dependent vasorelaxation in rat TA, MA and RA. STA-elicited arterial relaxations were reduced by NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) or the NO-sensitive guanylyl cyclase inhibitor 1H- [1, 2, 4] Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), but not by inducible iNOS inhibitor 1400 W nor the nonselective COX inhibitor indomethacin. Hcy caused eNOS uncoupling and decreases in NO, cGMP and BH4, which were attenuated by STA. Moreover, STA prevented decreases of GTPCH1 and DHFR levels in Hcy-treated BAECs.ConclusionWe demonstrated that STA effectively reversed the Hcy-induced endothelial dysfunction and prevented eNOS uncoupling by increasing the expression of GTPCH1 and DHFR. These results revealed a novel mechanism by which STA exerts its beneficial vascular effects.
Highlights
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs)
STA improved Hcy-impaired vascular relaxation In order to examine the effect of Hcy on vasorelaxation, rat thoracic aortas (TA), mesenteric arteries (MA) and renal arteries (RA) rings were incubated with Hcy (500 μM) or control medium for 1 h before measuring the ACh-induced endothelium-dependent relaxation
In uninjured rat TA, MA and RA, STA only slightly affected the vasorelaxation (Additional file 1: Figure S1A-C). These results suggest that STA protected endothelial function impaired by Hcy
Summary
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular diseases (CVDs). Stachydrine (STA) is an active component in Chinese motherwort Leonurus heterophyllus sweet, which has been widely used for gynecological and cardiovascular disorders. This study is aimed to examine the effects of STA on homocysteine (Hcy)-induced endothelial dysfunction. Stachydrine (STA) is a major constituent of Chinese motherwort Leonurus heterophyllus sweet, which has been used in traditional medicine to promote blood circulation and dispel blood stasis (Yin et al, 2010). Several studies have shown that STA has protective effects on vascular endothelial cells (ECs). STA protected endothelial against the injury induced by anoxia-reoxygenation (Yin et al, 2010). STA inhibited the deleterious effect of high glucose on ECs and acted through the modulation of SIRT1 pathway (Servillo et al, 2013). Little is known about STA on vascular relaxation, a common feature of endothelial function
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