ABSTRACT
Previous studies have found that Danhong injection (DHI), an extensively used herbal extract preparation in China, might be a powerful vasodilator. The aims of this study were to determine the vascular activity of DHI and its effects on arteries of different sizes. The results showed that DHI significantly inhibited rat-hindquarters and rabbit-ear vasoconstriction elicited by norepinephrine (NE) perfusion and markedly relaxed KCl-contracted and NE-contracted rat abdominal aortic and mesenteric artery rings. The endothelium made only a minor contribution to the vasorelaxant effect of DHI on artery segments. The vasorelaxant effect of DHI varied with the artery size, with larger arteries exhibiting a more sensitive and potent vasodilator response. DHI relaxed NE-induced vasoconstriction probably through inhibition of the intracellular Ca2+ release through the inositol triphosphate receptor system in the abdominal aorta and mesenteric artery, along with blockage of extracellular Ca2+ influx through the receptor-linked Ca2+ channels in the mesenteric artery. In addition, DHI completely relaxed KCl-induced contraction in both of the arteries, suggesting that inhibition of Ca2+ influx through voltage-gated Ca2+ channels is involved in the vasorelaxant effect of DHI. This elucidation of the vascular effects of DHI and the underlying mechanisms could lead to improved clinical applications.
Subject(s)
Aorta, Abdominal/drug effects , Drugs, Chinese Herbal/pharmacology , Mesenteric Arteries/drug effects , Vasodilation/drug effects , Animals , Aorta, Abdominal/metabolism , Calcium/metabolism , Calcium Channels/drug effects , Calcium Channels/metabolism , Drugs, Chinese Herbal/administration & dosage , Female , Male , Mesenteric Arteries/metabolism , Norepinephrine/pharmacology , Potassium Chloride/pharmacology , Rabbits , Rats , Rats, Sprague-Dawley , Vasoconstriction/drug effects , Vasodilator Agents/pharmacologyABSTRACT
OBJECTIVE: To study the effects of Danhong injection (DHI) on expression of the macrophage scavenger receptor 1 (MSR1) and ATP-binding cassette, sub-family A member 1 (ABCA1) genes, which encode scavenger receptor-A I (SR-AI) and ATP-binding cassette transporter 1 (ABCA1), respectively, as a potential anti-atherosclerotic mechanism. METHODS: Human U937 cells were stimulated by incubation with 100 nM phorbol 12-myristate 13-acetate (PMA) for 48 h. These stimulated, monocyte-like cells were then incubated for 24 h with 50 mg/L oxidized low-density lipoprotein (ox-LDL, to induce foam cell formation), together with a liver X receptor (LXR) agonist or with different DHI concentrations. MSR1 and ABCA1 mRNA levels were measured by fluorescence-based quantitative PCR. RESULTS: Compared with control cells (which received only ox-LDL), cells treated with both ox-LDL and 10 micromol/L LXR agonist showed lower MSR1 expression (but this effect was not statistically significant, P > 0.05) and higher ABCA1 expression (P < 0.01). Cells that received ox-LDL and 3 mL/L DHI possessed higher MSR1 mRNA levels than the controls, whereas cells treated with ox-LDL and higher DHI concentrations (10, 30 or 60 mL/L) showed lower MSR1 expression levels (but the differences observed between DHI concentration groups were not statistically significant, P > 0.05). ABCA1 expression in cells treated with ox-LDL and 3, 10 or 30 mL/L DHI was higher than in the control cells, and increased with increasing DHI concentration (P < 0.05). ABCA1 expression in cells treated with ox-LDL and the highest DHI concentration tested (60 mL/L) was not significantly different from that in the controls. ABCA1 mRNA levels in cells treated with ox-LDL and DHI were similar to, or lower than, those in cells treated with ox-LDL and the LXR agonist. CONCLUSION: DHI does not affect MSR1 mRNA levels in ox-LDL-treated U937 cells. However, at certain concentrations (10 and 30 mL/L), DHI significantly increases ABCA1 mRNA levels. Therefore, the anti-atherosclerotic action of DHI might be mediated by an increased expression of ABCA1.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Drugs, Chinese Herbal/pharmacology , Scavenger Receptors, Class A/genetics , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/metabolism , Gene Expression/drug effects , Humans , Scavenger Receptors, Class A/metabolism , U937 CellsABSTRACT
OBJECTIVE: To study the effect and mechanism of Danhong injection on isolated mesenteric arterial rings in rats. METHOD: An isolated vascular ring experiment was conducted to determine the changes in tension of vascular rings with a biological signal collection and analytical system. RESULT: Danhong injection had no impact on the tension of vascular rings. Danhong injection showed a significant vasodilatation effect on treated arteria rings of norepinephrine, and no remarkable impact was made on the effect without endothium. It showed notable effect on blood vessels treated with Ca(2+) and no significant impact on those treated with caffeine. It could inhibit NE-induced intracellular calcium from releasing and external calcium from inflowing. No effects of potassium channel blockers on aorta ring tensile force were found. CONCLUSION: Danhong injection shows significant vasodilation effect, which mainly works through vascular smooth muscle. Its vasodilation effect may be related to inhibitory receptor, voltage-dependent Ca(2+)-release and IP3 receptor-mediated Ca(2 +)-influx.
