Relaxant and Antioxidant Capacity of the Red Wine Polyphenols, Resveratrol and Quercetin

Relaxant and Antioxidant Capacity of the Red Wine Polyphenols, Resveratrol and Quercetin, on Isolated Mice Corpora Cavernosa

Charlotte Boydens, MSc; Bart Pauwels, MPharm; Kelly Decaluwé, PhD; Peter Brouckaert, MD, PhD; and Johan Van de Voorde PhD

ONLINE: December 2, 2014 – The Journal of Sexual Medicine

DOI: 10.1111/jsm.12786


Introduction

Resveratrol and quercetin are naturally occurring polyphenols found in red wine. They can relax arteries by activating the nitric oxide (NO)/soluble guanylyl cyclase (sGC) pathway.

However, part of this relaxation occurs independently of the NO/sGC pathway through the activation of different types of K+ channels.

Resveratrol and quercetin can also reduce oxidative stress.

Given these qualities, the two polyphenols could be helpful in treating erectile dysfunction (ED).

Aim of the Study

This study had two aims:

• To evaluate the extent of NO/sGC dependency in the relaxant capacity of resveratrol and quercetin on isolated mice corpora cavernosa
• To analyze the antioxidant capacity of both polyphenols in the presence and absence of palmitic acid (PA)

Materials and Methods

The animals involved in the study included:

• 143 adult male Swiss mice
• 15 129SvEvS7 sGC wild type (sGCα1+/+) mice
• 15 sGC alpha1 knockout (sGCα1−/−) mice

In their abstract, the authors described their methods as follows:

“Isolated mice aorta and CC were mounted for isometric tension recordings into organ baths. Cumulative concentration-response curves were constructed for resveratrol and quercetin in the absence/presence of inhibitors of the NO/sGC pathway. In addition, in CC the effect of resveratrol and quercetin was studied on NO-mediated relaxations using acetylcholine (Ach), sodium nitroprusside (SNP), and electrical field stimulation (EFS). In certain experiments, corporal tissues were exposed to oxidative stress using palmitic acid (PA, 0.5 mM).”

Results

Both resveratrol and quercetin relaxed aortas in the Swiss mice. However, in the corpora cavernosa, only resveratrol was able to evoke concentration-dependent relaxations.

The NO/sGC pathway was further investigated in the sGCα1−/−) mice. Quercetin- and resveratrol-induced relaxations in the aortas of these mice were significantly diminished when compared to the sGCα1+/+ controls, indicating NO/sGC dependency.

However, resveratrol-induced relaxations of the CC in the sGCα1−/− mice were not decreased compared to the controls.

The involvement of potassium channels was also investigated. Higher K+ concentrations did not alter the corporal responses to resveratrol.

To study the effect of neuronal NO, nerves were stimulated with EFS. This technique relaxed CC in a frequency-dependent manner, but the relaxations were not influenced by the presence of resveratrol or quercetin.

Pretreatment with palmitic acid reduced the EFS-evoked relaxations. Co-administration of quercetin reversed PA-decreased EFS relaxations, but co-administration of resveratrol restored PA-induced EFS responses to the level of controls.

Discussion

The authors characterized their findings as twofold:

• Resveratrol, but not quercetin, relaxes isolated mice CC in a concentration-dependent manner through mechanisms independent of NO/sGC.
• Resveratrol is more potent than quercetin in reversing PA-induced decrease in nNOS responses.

Both polyphenols are “potent vasodilators” of mice aorta, but only resveratrol can induce corporal relaxation.

The authors explained that the failure of quercetin to relax mice CC in comparison to human CC may be explained by species differences, a different molecular target, and structural features.

The contribution of the NO/sGC pathway in the relaxant effect of resveratrol on mice CC is unknown, the authors stated.

The study results suggest “a NO/sGC-independent mechanism of resveratrol to relax mice CC.” But the mechanism by which resveratrol relaxes mice CC is unclear.

“In our study, neither resveratrol nor quercetin enhanced endogenously (Ach), exogenously (SNP), or neuronal (EFS) NO-mediated relaxation responses of CC,” the authors wrote. “This could imply that a certain amount of oxidative stress is required in order for quercetin or resveratrol to exert their beneficial effect.”

They added that PA “causes only a low degree of oxidative stress, which was too low to impair Ach or SNP responses.”

The authors pointed out that their research was conducted in vitro, so their results could not be applied to in vivo situations. It is uncertain whether the results could be reproduced in vivo. Also, hormonal status could play a role in the responsiveness of corporal tissues and, in turn, the responsiveness of resveratrol.

Another limitation was the lack of direct measurement of the effect of resveratrol and quercetin on oxidative stress.

In their conclusion, the researchers offered implications for the treatment of ED, although more research is needed:

“It is necessary to consider backup therapeutic approaches in the treatment of ED as specific patient populations are refractory to first-line therapy with phosphodiesterase type 5 (PDE5) inhibitors [19]. In this perspective, our results demonstrate that resveratrol, a naturally occurring polyphenol with direct relaxant and antioxidant effects on mice CC, is potentially beneficial for patients suffering from ED. Still, additional pharmacological and toxicological research is needed to elucidate whether resveratrol also exerts these relaxant and antioxidant properties in vivo, and thus possesses strong therapeutic value for patients suffering from ED.”