Short- and long-term effects of ferulic acid on blood pressure in spontaneously hypertensive rats

Abstract

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phenolic compound contained in rice bran and other plants. The effect of ferulic acid on blood pressure (BP) was investigated in spontaneously hypertensive rats (SHR). After oral administration of ferulic acid (1 to 100 mg/kg) to SHR, systolic blood pressure (SBP) significantly decreased in a dose-dependent manner. When oral ferulic acid (50 mg/kg) was administered to SHR, BP was lowest at 1 h and returned to basal levels at 6 h. There was a significant correlation between SHR plasma ferulic acid and changes in the SBP of the tail artery, suggesting that absorbed ferulic acid reduces BP. When 7-week-old SHR were given 10 and 50 mg/kg/d of ferulic acid for 6 weeks, increases in BP were significantly attenuated compared to SHR on the control diet. Intravenous injection of ferulic acid dose dependently reduced carotid arterial pressure in anesthetized SHR. Furthermore, the depressor effect of intravenous ferulic acid (1 mg/kg) was significantly attenuated by pretreatment of SHR with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 3 mg/kg, administered intravenously). These data suggest that the hypotensive effect of ferulic acid in SHR is associated with NO-mediated vasodilation.

Effects of ferulic acid on diabetic nephropathy in a rat model of type 2 diabetes

“…These effects may be a suppression of the ROS by FA treatments. These studies reported that FA treatment effectively decreased blood pressure levels (Suzuki et al, 2002). We used OLETF rats to determine whether FA has beneficial effects in type 2 diabetic rats.…”

“…Previous studies reported that FA is an antioxidant that neutralizes free radicals such as superoxide, nitric oxide and hydroxyl radicals that may cause oxidative damage to cell membranes and DNA (Kanski et al, 2002;Ha et al, 2008). FA provides meaningful synergistic protection against oxidative stress in the skin and should protect against photoaging and skin cancer (Lin et al, 2005), hypoglycemic and hypolipidemic effects (Sri Balasubashini et al, 2003;Ohnishi et al, 2004;Jung et al, 2007), hypotensive effects (Suzuki et al, 2002), and anti-inflammatory effects (Yagi and Ohishi, 1979).…”

Antihypertensive effects and mechanisms of chlorogenic acids

“…18 Oral administration of 50 mg kg À1 of ferulic acid also induced anti-hypertensive effect in both SHR and stroke-prone SHR (that is, SHRsp) models. 14,41 After digestion of ferulic acid in doses ranging from 0.5 to 50 mM, plasma levels of ferulic acid were elevated, with negatively correlated SBP changes ranging from À5 mm Hg to À15 mm Hg. 14 This evidence suggests that the CGA metabolites ferulic acid and, to a lesser extent, caffeic acid are responsible for the hypotensive effect seen in oral administration of CGA.…”

“…51 As discussed earlier, of the CGA metabolites, ferulic acid had greatest effect on BP reduction. 14,18 Interestingly, ferulic acid contained an ortho-methoxy-substituted-catechol structure (apocynin analogous) and had been implicated to work as a non-selective NAD(P)H oxidase antagonist by reacting with sulfhydryl groups. 52,53 In aortic rings pre-contracted with phenylephrine (an alpha-adrenergic neurotransmitter agonist), the administration of ferulic acid greatly increased NO bioavailability and enhanced acetylcholineinduced endothelial-dependent vasodilation, 35 but had no effect on sodium nitroprusside (a direct NO donor)-induced endotheliumindependent vasodilation, 19,35 signifying that vascular integrity (in particular intact endothelium) is essential for CGAs to lower BP.…”

“…9,10 In some animal studies, CGAs have also been shown to sensitize insulin action, and to improve glucose tolerance and lipid metabolism. [11][12][13] Of great interest, investigations during the last decade have demonstrated that the consumption of green coffee extracts produces an anti-hypertensive effect in both rats and humans, 14,15 as a result of improved endothelial or vascular function. 16,17 Such biological effects have been attributed to the presence of CGAs in green coffee.…”