Mechanisms for antihypertensive effect of CocoanOX, a polyphenol-rich cocoa powder, in spontaneously hypertensive rats

Abstract

We investigate the mechanisms involved in the long-term antihypertensive effect of a polyphenol-rich cocoa powder, named CocoanOX® (CCX), in spontaneously hypertensive rats (SHR). We have carried out two different batches of experiments. For the first batch of experiments, forty 3week-old male SHR were randomly divided with ad libitum intake into four groups of 10 animals, that respectively received the following drinking fluids up to the 20th week of life (treatment period): tap water (control), CCX 100mg/kg/day, CCX 200mg/kg/day and CCX 400mg/kg/day. Five 20week-old rats of each group were sacrificed by decapitation. From the 20th to 24th week of life all the remaining animals were given tap water (follow-up period), and all of them were sacrificed at the end of the follow-up period. Plasma malondialdehyde (MDA), reduced glutathione in the liver, plasma and aorta angiotensin converting enzyme (ACE) activity and plasma angiotensin II were determined in all the sacrificed SHR that were included in this batch of experiments. Plasma MDA decreased and liver reduced glutathione increased in the 20week-old CCX treated SHR. These effects were not observed in the rats that were sacrificed after the follow-up period. CCX treatment did not modify aorta ACE activity, but the activity of ACE and the levels of angiotensin II increased in the plasma of the SHR treated with the highest dose of CCX. ACE activity returned to basal values in the SHR that were sacrificed after the follow-up period. However, angiotensin II levels were slightly higher after withdrawal of CCX.For the second batch of experiments we used aorta rings obtained from untreated SHR, and we evaluated the relaxation caused by CCX in different aorta preparations. CCX relaxed the intact aorta preparations but this cocoa did not relax the endothelium-denuded aorta rings from the untreated SHR. l-NAME, but not indomethacin, inhibited the relaxation caused by CCX in the SHR aorta rings. We postulate that the antihypertensive effect of CCX might be mediated by an improvement of endothelial release of nitric oxide and by a reduction of oxidative stress. The inhibition of ACE could be implicated in the antihypertensive effect of CCX.