Resveratrol Improves Cardiovascular Function in DOCA-Salt Hypertensive Rats

Abstract

The phytoalexin resveratrol (3,4',5-trihydroxy-trans-stilbene) may attenuate cardiovascular disease in man. This study has determined whether treatment with resveratrol (1 mg/kg/day orally) prevented cardiac fibrosis and the decreased cardiovascular function in the DOCA-salt hypertensive rat as a model of human hypertension. Uninephrectomised rats (UNX) administered DOCA (25mg every 4th day sc) and 1% NaCl in drinking water for 28 days developed cardiac and vascular remodelling. In these DOCA-salt rats, resveratrol decreased inflammatory cell infiltration, decreased cardiac fibrosis (left ventricular interstitial and perivascular collagen content) and improved cardiac and vascular function. Resveratrol attenuated other features of cardiovascular remodelling such as increases in systolic blood pressure, left ventricular wet weight, left ventricular wall thickness, diastolic stiffness constant, as well as decreased cardiac contractility and prolonged action potential duration characteristic of DOCA-salt rats. In summary, resveratrol, at a nutritionally relevant dose, prevents or attenuates the adverse changes in the cardiovascular system. We propose that the anti-inflammatory and anti-fibrotic effects of resveratrol are responsible, at least in part, for its amelioration in cardiovascular remodelling in DOCA-salt rats. These actions of resveratrol could play an important role in the protective effects on the human cardiovascular system reported for this constituent of red wine.

Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats

“…STZ-induced DM is known to increase oxidative stress and subsequently impair endothelial and smooth muscle function in isolated thoracic aortas (51)(52)(53) . Consistent with these findings, we observed significantly reduced endothelium-dependent and endothelium-independent relaxation in thoracic aortic rings isolated from STZ rats.…”

Why research on resveratrol-mediated cardioprotection should not decelerate1This editorial was invited by the Editors.

“…These include the following: (i) hypertension (Liu et al 2005;Dolinsky et al 2009;Thandapilly et al 2010;Toklu et al 2010;Wojciechowski et al 2010;Chan et al 2011;Rimbaud et al 2011); (ii) obesity (Louis et al 2011;Qin et al 2012 (Barger et al 2008). There is also one study that reported cardioprotection in an animal model of heart failure (Tanno et al 2010).…”

“…The average recommended dose of red wine is 2 glasses (approximately 300 mL, which is a conservative estimate), and it has been recently reported that some red wines may contain as much as 40-50 mg resveratrol per litre (Gonçalves and Camara 2011). This would equate to a dose of as much as 15 mg resveratrol in 300 mL of wine, which is slightly lower than that used to improve cardiac structure and function in animal models of ischemic heart disease and hypertension in 2 above-mentioned studies (Chan et al 2011;Lin et al 2008). The dose used in those animal studies was •day -1 (Lin et al 2008;Chan et al 2011).…”

“…This would equate to a dose of as much as 15 mg resveratrol in 300 mL of wine, which is slightly lower than that used to improve cardiac structure and function in animal models of ischemic heart disease and hypertension in 2 above-mentioned studies (Chan et al 2011;Lin et al 2008). The dose used in those animal studies was •day -1 (Lin et al 2008;Chan et al 2011). The lone successful human heart failure clinical trial was also achieved with a dosage of 10 mg resveratrol per day.…”

“…The lone successful human heart failure clinical trial was also achieved with a dosage of 10 mg resveratrol per day. Despite concerns regarding the bioavailability of resveratrol, these studies (Lin et al 2008;Chan et al 2011;Magyar et al 2012) indicate that a very low dose of resveratrol, which could be achieved through dietary intake, can confer beneficial effects on the heart. In summary, despite the ill-fated incident (the UC report) that has cast doubt on the validity of resveratrol and heart research, as well as its researchers throughout the world, there is sufficient evidence from intact organ and animal studies to support a claim for cardioprotection by resveratrol in different forms of heart disease (Penumathsa and Maulik 2009;Chu et al 2011;Wang et al 2011;Wu and Hsieh 2011;Li et al 2012).…”