Dietary fat contributes to the elevation of blood pressure and increases the risk of stroke and coronary artery disease. Previous observations have shown that voltage-gated Ca(2+) current density is significantly increased in hypertension and can be affected by free fatty acids (FAs). We hypothesized that a diet of elevated fat level would lead to an increase in blood pressure, an elevation of L-type Ca(2+) current, and an increase in saturated FA content in vascular smooth muscle cell membranes. Male Osborne-Mendel rats were fed normal rat chow or a high-fat diet (Ob/HT group) for 8 weeks. Blood pressures in the Ob/HT group increased moderately from 122.5+/-0.7 to 134.4+/-0.8 mm Hg (P<0.05, n=26). Voltage-clamp examination of cerebral arterial cells revealed significantly elevated L-type Ca(2+) current density in the Ob/HT group. Voltage-dependent inactivation of the Ob/HT L-type channels was significantly delayed. Total serum FA contents were significantly elevated in the Ob/HT group, and HPLC analyses of fractional pools of FAs from segments of abdominal aorta revealed that arachidonic acid levels were elevated in the phospholipid fraction in Ob/HT. No differences in vascular membrane cholesterol contents were noted. Plasma cholesterol was significantly elevated in portal venous and cardiac blood samples from Ob/HT rats. These findings suggest that an elevation of plasma FAs may contribute to the development of hypertension via a process involving the elevation of Ca(2+) current density and an alteration of channel kinetics in the vascular smooth muscle membrane.