Diets high in polyphenols may protect estrogen-depleted womenand rats from hypertension, but there is little evidence for this beneficial effect in males. On a polyphenol-free diet, ovariectomized spontaneously hypertensive rats (SHRs), high dietary NaCl increases arterial pressure, and this effect is greatly blunted by a soy-based diet. High NaCl diets also elevate arterial pressure in male SHRs, and pilot studies indicated that soy polyphenols blunt this effect. The present studies tested the hypothesis that genistein (the primary polyphenol in soy) reduces NaCl-sensitive hypertension in young, male stroke-prone SHRs (SHR-SP, a very NaCl-sensitive strain of SHR). Seven-week-old male SHR-SPs were placed on polyphenol-free diets with or without normal dietary amounts of genistein [0.06% (wt/wt)] and containing high (4%), moderate (2%), or basal (0.7%) NaCl. SHR-SP on the genistein-free diet displayed a dose-related increase in arterial pressure in response to dietary NaCl, and dietary genistein blunted this response. Ganglionic blockade with hexamethonium reduced arterial pressure to similar levels in all six groups, suggesting that the antihypertensive effects of genistein are influenced by the autonomic nervous system.We further hypothesized that genistein, like estrogen, would improve insulin sensitivity and lipid profiles. Thus, in study 2, 7-wk-old male SHR-SP were placed on high (6%) or basal (0.7%) NaCl diets with or without genistein (0.06%). Dietary genistein reduced plasma insulin and insulin resistance in SHR-SP on a high NaCl diet and decreased plasma cholesterol and triglycerides in SHR-SP on the basal NaCl diet. Thus, in male SHR-SP, dietary genistein blunts NaCl-sensitive hypertension, and these effects may be regulated, in part, by the autonomic nervous system and/or metabolic mechanisms. Copyright © 2007 by The Endocrine Society.