Hirafuji M, Ebihara T, Kawahara F, Tsunoda M, Hamaue N, Tanimura A, Minami M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Nihon Yakurigaku Zasshi. 1997 Oct;110 Suppl 1:171P-176P. doi: 10.1254/fpj.110.supplement_171.
There are increasing evidences that fish oil-enriched diets attenuate the progression of several types of human and experimental renal, intestinal and cardiovascular disorders including hypertension. Docosahexaenoic acid (DHA) may be one of the active biological component. We previously reported that dietary DHA suppressed the progression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). The purpose of this study was to clarify the in vitro effect of DHA on vascular smooth muscle cell functions such as cell growth, hypertrophy, NO release, and intracellular Ca+2 dynamics which involves in the regulatory mechanisms of vascular tone. Addition of DHA to the culture medium of aortic smooth muscle cells isolated from SHRSP and normotensive Wistar Kyoto rats (WKY) had no significant effects on the cell growth, and cell hypertrophy induced by angiotensin II as measured by flow cytometer. DHA did not have a significant effect on interleukin-1 beta (10 ng/ml)-induced nitric oxide release from smooth muscle cells of SHRSP. However, the treatment of smooth muscle cells with DHA (30 microM) for 2 days significantly suppressed the increase in the intracellular Ca2+ concentration induced by 5-hydroxytryptamine, angiotensin II, depolarizing concentration of KCl, but not by thapsigargin. This suppression seems to be due to the suppression of Ca2+ influx, as determined by Mn2+ influx experiment. These results suggest that DHA specifically suppresses receptor-mediated Ca2+ influx in smooth muscle cells. This may be one of the mechanisms by which dietary DHA prevents the development of hypertension in SHRSP.
越来越多的证据表明，富含鱼油的饮食可减缓包括高血压在内的几种人类和实验性肾脏、肠道及心血管疾病的进展。二十二碳六烯酸（DHA）可能是其中一种具有活性的生物成分。我们之前报道过，饮食中的DHA可抑制易卒中型自发性高血压大鼠（SHRSP）的高血压进展。本研究的目的是阐明DHA对血管平滑肌细胞功能的体外作用，如细胞生长、肥大、一氧化氮释放以及细胞内Ca+2动态变化，这些均涉及血管张力的调节机制。向从SHRSP和正常血压的Wistar Kyoto大鼠（WKY）分离的主动脉平滑肌细胞培养基中添加DHA，对细胞生长以及通过流式细胞仪测量的血管紧张素II诱导的细胞肥大没有显著影响。DHA对SHRSP平滑肌细胞中白细胞介素-1β（10 ng/ml）诱导的一氧化氮释放没有显著影响。然而，用DHA（30 microM）处理平滑肌细胞2天可显著抑制5-羟色胺、血管紧张素II、去极化浓度的KCl诱导的细胞内Ca2+浓度升高，但对毒胡萝卜素诱导的升高无抑制作用。如通过Mn2+内流实验所确定的，这种抑制似乎是由于Ca2+内流的抑制。这些结果表明，DHA特异性抑制平滑肌细胞中受体介导的Ca2+内流。这可能是饮食中的DHA预防SHRSP高血压发生的机制之一。
