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

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.

Danhong Injection Protects Against Hypertension-Induced Renal Injury Via Down-Regulation of Myoglobin Expression in Spontaneously Hypertensive Rats

“…2017) [27], Losartan (positive control drug) dramatically lowered diastolic, systolic, and mean BP in SHR starting from day 1 till after 4 weeks ( *p < 0.05 vs SHR), we also found that treatment with DHI had no such immediate and aggressive effect on BP reduction in SHR as observed with Losartan, however diastolic, systolic, and mean BP were all significantly decreased compared to those of saline controls within 7 days till 4 weeks. The BP reduction effects of Danhong injection is associated in-path to the amelioration of vascular remodeling and up-regulation of the Kallikrein-kinin system.…”

“…Previously, we found that DHI reversed vascular remodeling and exerted an antihypertensive effect through the Kallikrein-kinin system up-regulation in SHR [27]. In this present study, we now show that treatment with DHI/Losartan significantly reversed hypertension-induced kidney injury including renal injury biomarker KIM-1 and also provided renal-injury related genes suppression, particularly a down-regulation of renal myoglobin (Mb) gene expression confirmed by qRT-PCR and Western blot analysis.…”

“…Invasive BP where measured using ADInstruments PowerLab 8/30 connected to bridge Amp ML 221 as previously reported [27]. Invasive BP was recorded after rats were treated with DHI and a change in BP was observed.…”

“…Noninvasive tail-cuff blood pressure (BP) measurements were performed on conscious rats every two days for 4 weeks after the initiation of the drug treatments using an 8-channel CODA noninvasive BP acquisition system (Kent Scientific Corporation, CT USA) as previously reported [27]. Systolic, diastolic, and mean BP as well as heart rate was recorded.…”

“…Study has shown that DHI can significantly reduce plasma levels of endothelin-1, soluble P-selectin and high sensitive C-reactive protein in acute coronary syndrome patients, [25] and improves cardiac remodeling to preserve ventricular function in post-myocardial infarction rats [26]. In the previous study, we showed that DHI exerted an antihypertensive effect and vascular protection in SHR [27]. However, whether DHI has renal protective effect has not been explored.…”