High-fat diet elevates blood pressure and cerebrovascular muscle Ca2+ current

Dietary fat contributes to the elevation of blood pressure and increases th e risk of stroke and coronary artery disease, Previous observations have sh own that voltage-gated Ca2+ current density is significantly increased in h ypertension 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 pressu re, an elevation of L-type Ca2+ current, and an increase in saturated FA co ntent in vascular smooth muscle cell membranes. Male Osborne-Mendel rats we re 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 134.3 +/-0.8 mm Hg (P<0.05, n = 26). Voltage-clamp examination of cerebral arteri al cells revealed significantly elevated L-type Ca2+ current density in the Ob/HT group. Voltage-dependent inactivation of the Ob/HT L-type channels w as significantly delayed. Total serum FA contents were significantly elevat ed in the Ob/HT group, and HPLC analyses of fractional pools of FAs from se gments of abdominal aorta revealed that arachidonic acid levels were elevat ed in the phospholipid fraction in Ob/HT. No differences in vascular membra ne cholesterol contents were noted. Plasma cholesterol was significantly el evated in portal venous and cardiac blood samples from Ob/HT rats. These fi ndings suggest that an elevation of plasma FAs may contribute to the develo pment of hypertension via a process involving the elevation of Ca2+ current density and an alteration of channel kinetics in the vascular smooth muscl e membrane.