High-fat diet elevates blood pressure and cerebrovascular muscle Ca(2+) current.
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.
Wilde
D W
DW
Bristol-Myers Squibb, US Pharmaceuticals, Ann Arbor, MI 48105, USA. dwwilde@hotmail.com
Massey
K D
KD
Walker
G K
GK
Vollmer
A
A
Grekin
R J
RJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D004041:Dietary Fats / Q000494:pharmacology*; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000032:analysis / Q000097:blood; D006949:Hyperlipidemias / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D015640:Ion Channel Gating / Q000502:physiology; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology; D018408:Patch-Clamp Techniques; D051381:Rats; D011919:Rats, Inbred Strains
D015220:Calcium Channels; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D002784:Cholesterol; D002118:Calcium