Involvement of nitric oxide and prostacyclin in the antihypertensive effect of low-molecular-weight procyanidin rich grape seed extract in male spontaneously hypertensive rats

The aim of this study was to evaluate the involvement of endothelial-relaxing factors as possible antihypertensive mechanism of low-molecular-weight procyanidin rich grape seed extract (LM-GSPE). Thirty 17-20-week-old male spontaneously hypertensive rats (SHR) were administered water or 375 mg/kg LM-GSPE by intragastric gavage. One millilitre of saline, 30 mg/kg NG-Nitro-l-arginine methyl ester (l-NAME) or 5 mg/kg indomethacin was administrated intraperitoneally. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded before and 6 h after oral administration. Plasma concentration of 6-keto-prostaglandin F1α (PGF1α) was quantified. In addition, we evaluated the relaxation caused by LM-GSPE in different aorta preparations. The antihypertensive effect of LM-GSPE was completely and partially abolished by l-NAME and indomethacin, respectively. In addition, plasma PGF1α was increased in LM-GSPE-administered rats. Finally, LM-GSPE relaxed the intact aorta preparations but did not relax the endothelium-denuded aorta rings. l-NAME inhibited the relaxation caused by LM-GSPE in the SHR aorta rings, but indomethacin did not. Therefore, the antihypertensive effect of LM-GSPE in SHR is endothelium dependent, and it could be mediated by changes in endothelium-derived nitric oxide bioavailability. Nevertheless, prostacyclin could also contribute additionally to this effect.