Long-term effects of a low dosage of grape seed proanthocyanidin extract on blood pressure in spontaneously hypertensive rats

Most studies on the antihypertensive effects of bioflavonoids have reported short-term effects (within 7 weeks) at high concentrations (40-100 mg kg ^-1 day^-1). The present study by contrast has investigated long-term effects of low concentrations of bioflavonoids on arterial blood pressure and left ventricular performance in spontaneously hypertensive rats (SHR). Spontaneously hypertensive rats were divided into a treated (n = 16) and a control (n = 16) group. The treated group received daily a grape seed proanthocyanidin extract (GSPE) at a concentration of 4 mg kg^-1 day^-1 over six months. Arterial blood pressure (ABP) was measured once monthly on six randomly selected rats from both groups using an indirect tail-cuff method. After three months, the remaining rats underwent catheterizatlons to measure left ventricular performance and aortic pressure. The possible role of nitric oxide (NO) in the effects of GSPE was investigated by blocking NO synthase with N-nitro-L-arginine methyl ester (L-NAME). Animals in the treated group had significantly lower arterial end-diastolic pressures (AEDP) after three months of treatment compared with control animals, and this trend continued until six months. In the treated group, left ventricular systolic pressures (LVSP) were reduced by 16.6% (P = 0.005), their dP/dt, _max (left ventricular pressures) were reduced by 19.7% (P = 0.050), and cardiac work was reduced by 22.0% (P = 0.045) at the end of three months. Treatment with L-NAME suggested a contribution of NO to the effects of GSPE on blood pressure. A low concentration of GSPE administered over six months lowered AEDP significantly, and the L-NAME response suggested that NO is involved. The decreased AEDP had a lowering effect on left ventricular dynamics of hypertensive rats.