Danhong injection reduces vascular remodeling and up-regulates the Kallikrein-kinin system in spontaneously hypertensive rats

Abstract

Abstract Although Danhong injection (DHI) is one of the most prescribed cardiovascular medicines in China, its therapeutic indications and mechanisms remain partially defined. We now identify molecular targets of DHI in resistance vasculatures and demonstrate its role in vascular function and blood pressure (BP) regulation. BP was determined in DHI, Losartan, and placebo- treated Spontaneously Hypertensive Rats (SHR) by both noninvasive and invasive measurements. Vasorelaxation was examined both in conduit and resistance vasculature by ex vivo aortic rings. Microarray analysis was performed and gene expression changes were verified by RT-qPCR and ELISA. Diastolic, systolic and mean BPs were significantly lower in DHI-treated SHR than controls by both tail-cuff and invasive BP measurements. In ex vivo rings, aortic and mesenteric vessels from SHR treated with DHI exhibited significantly greater acetylcholine-mediated relaxation. Among the 282 genes that are differentially expressed in microarray analysis, DHI treatment up-regulated the expression of kallikrein and plasma kallikrein B genes. DHI also significantly increased serum kallikrein content in SHR. Treatment with DHI significantly increased the ratio of aortic lumen to outer diameter. Therefore, the reduction of vascular remodeling and the up-regulation of Kallikrein-kinin system contribute, at least in part, to the antihypertensive effect of DHI in SHR.