Quercetin Enhances Gastric Nitric Oxide Formation and Potentiates the Antihypertensive Effects of Oral Nitrite Administration

Oral nitrite supplementation enhances nitric oxide (NO) bioavailability and lowers blood pressure. Quercetin may facilitate the reduction of nitrite to NO. However, the combined effects of nitrite and Quercetin on gastric NO formation and blood pressure have not been explored. We investigated whether oral treatment with Quercetin enhances the gastric conversion of nitrite to NO (in vitro and in vivo) and exerts antioxidant and antihypertensive effects. Spontaneously hypertensive rats (SHR) were divided into six groups (n = 6/group): three groups treated with Quercetin 10 mg/kg followed 15 min later by water, nitrite 1 mg/kg (nonantihypertensive) or 15 mg/kg (antihypertensive) by gavage, and three similar control groups treated with vehicle, followed by the same nitrite treatments. Blood pressure, gastric NO, plasma nitrite, nitrate, nitrosylated species (RxNO) and aortic S-nitrosylated proteins were measured. Oxidative stress was also assessed. Quercetin treatment converted a nonantihypertensive dose of nitrite into an effective antihypertensive intervention in association with increased in vitro and in vivo gastric NO formation. However, Quercetin did not enhance nitrite-induced increases in systemic or vascular nitrite, nitrate, RxNO concentrations nor vascular protein nitrosation. Our results show that Quercetin is a potent enhancer of gastric NO formation from nitrite and amplifies its antihypertensive effects. This combination of drugs may represent a safe and effective therapeutic strategy.