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(Hypertension. 2000;35:832.)
© 2000 American Heart Association, Inc.

Scientific Contributions

High-Fat Diet Elevates Blood Pressure and Cerebrovascular Muscle Ca²⁺ Current

Dixon W. Wilde; Kenneth D. Massey; Glenn K. Walker; Alan Vollmer; Roger J. Grekin

From Bristol-Myers Squibb (D.W.W.), US Pharmaceuticals, Ann Arbor, Mich; Warner-Lambert/Parke-Davis Pharmaceuticals (K.D.M.), Ann Arbor, Mich; Department of Biology (G.K.W.), Eastern Michigan University, Ypsilanti, Mich; and Veterans Administration Medical Center (A.V., R.J.G.), Ann Arbor, Mich.

Correspondence to Dixon W. Wilde, PhD, Bristol-Myers Squibb, US Pharmaceuticals, 4701 Parkside Ct, Ann Arbor, MI 48105. E-mail dwwilde{at}hotmail.com

Abstract—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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ current density and an alteration of channel kinetics in the vascular smooth muscle membrane.

Key Words: hypertension, obesity • calcium • ions • hyperlipidemia • obesity • chromatography

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