EFFECT OF A NITRIC OXIDE-RELEASING NAPROXEN DERIVATIVE ON HYPERTENSION AND GASTRIC DAMAGE-INDUCED BY CHRONIC NITRIC-OXIDE INHIBITION IN THERAT

NSAIDs can elevate blood pressure through mechanisms such as renal vas oconstriction and sodium retention. These effects are particularly evi dent in hypertensive individuals. Nitric oxide-releasing NSAID derivat ives have been shown to have greatly reduced toxicity in the gastroint estinal tract and kidney. We therefore evaluated the effects of a 4 we ek treatment with either naproxen or its nitric oxide-releasing deriva tive (NO-naproxen) on systemic arterial blood pressure and gastric dam age in rats in which hypertension was induced by L-NAME. Rats received either L-NAME dissolved in the drinking water (400 mg/L) or tap water (control). Vehicle, naproxen (10 mg/kg) or an equimolar dose of NO-na proxen (14.5 mg/kg) were administered orally each day. After 4 weeks, blood pressure was measured, blood samples were taken for measurement of thromboxane synthesis, and gastric damage was evaluated by blind, m acroscopic scoring. Both naproxen and NO-naproxen inhibited systemic c yclooxygenase activity by >90%. NO-naproxen-treated rats exhibited no significant gastric damage. The gastric damage produced by L-NAME alon e was potentiated by naproxen but prevented by NO-naproxen. L-NAME tre atment significantly increased blood pressure. In the absence of L-NAM E, the naproxen group had significantly higher blood pressure than bot h the control and NO-naproxen groups. In rats receiving L-NAME, the sa me conclusions apply, but the concomitant administration of NO-naproxe n was able to significantly reduce the blood pressure compared to L-NA ME alone. Based on these results, we conclude that NO-naproxen may rep resent a safer alternative to standard NSAIDs in the treatment of infl ammatory conditions in hypertensive patients. (C) 1998 Elsevier Scienc e Inc.