Abstract
Nitric oxide (NO) is released by endothelial cells in the blood vessel wall to enhance vasodilation. Marine polyphenols are known to have protective effects against vascular dysfunction and hypertension. The present study is the first to investigate how diphlorethohydroxycarmalol (DPHC) isolated from Ishige okamurae affects calcium levels, resulting in enhanced vasodilation. We examined calcium modulation with the well-known receptors, acetylcholine receptor (AchR) and vascular endothelial growth factor 2 (VEGFR2), which are related to NO formation, and further confirmed the vasodilatory effect of DPHC. We confirmed that DPHC stimulated NO production by increasing calcium levels and endothelial nitric oxide synthase (eNOS) expression. DPHC affected AchR and VEGFR2 expression, thereby influencing transient calcium intake. Specific antagonists, atropine and SU5416, were used to verify our findings. Furthermore, based on the results of in vivo experiments, we treated Tg(flk:EGFP) transgenic zebrafish with DPHC to confirm its vasodilatory effect. In conclusion, the present study showed that DPHC modulated calcium transit through AchR and VEGFR2, increasing endothelial-dependent NO production. Thus, DPHC, a natural marine component, can efficiently ameliorate cardiovascular diseases by improving vascular function.
Highlights
Hypertension is a medical condition characterized by persistently high pressure on the blood vessels [1]
We found that DPHC was not toxic when used at concentrations of 6, 20, and 60 μM, but upon treatment with 100 μM DPHC, the cell viability was slightly decreased
Nitric oxide (NO) production levels were significantly increased starting from 30 min, and the peak was observed at 24 h (Figure 2a)
Summary
Hypertension is a medical condition characterized by persistently high pressure on the blood vessels [1]. The higher the pressure, the more the heart has to pump to overcome the resistance from blood vessels due to the blood pressure [2]. Vasodilation plays a vital role in preventing hypertension. Nitric oxide (NO) release by endothelial cells in the blood vessel wall has been reported to improve vascular tone [3]. It is widely accepted that NO, along with the endothelium-derived relaxing factor [4], exerts vasodilatory and antiproliferative effects to maintain vascular homeostasis. NO is synthesized by the endothelial nitric oxide synthase (eNOS), which is activated by blood shear-stress and agonists such as acetylcholine [5]
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