Dahl salt-sensitive rats are protected against vascular defects related to diet-induced obesity.
Obesity increases plasma renin activity and angiotensin II levels, leading to vascular damage, elevated blood pressure, diabetes mellitus, and renal damage. Because genetic deletion of crucial parts of the renin-angiotensin system protect against obesity-related cardiovascular defects, we hypothesized that Dahl salt-sensitive (SS) rats, a model of chronically low plasma renin activity and angiotensin II levels, would be protected against vascular defects during diet-induced obesity compared with SS.13(BN) consomic rats showing normal renin-angiotensin system regulation. We evaluated vascular function in middle cerebral arteries of SS or SS.13(BN) rats fed high-fat (45% kcal from fat) versus normal-fat diet for 15 to 20 weeks from weaning. Endothelium-dependent relaxation in response to acetylcholine (10(-8) to 10(-4) mol/L) was restored in middle cerebral arteries of high-fat SS rats versus normal-fat diet controls, whereas vasodilation to acetylcholine was dramatically reduced in high-fat SS 13(BN) rats versus normal-fat diet controls. These findings support the hypothesis that physiological levels of angiotensin II play an important role in maintaining normal vascular relaxation in cerebral arteries and suggest that the cerebral vasculature of the SS rat model is genetically protected against endothelial dysfunction in diet-induced obesity.
Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. abeyer@mcw.edu
Andreas M
AM
Beyer
Gabor
G
Raffai
Brian
B
Weinberg
Katherine
K
Fredrich
Julian H
JH
Lombard
D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D004435:Eating / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000502:physiology*; D009765:Obesity / Q000139:chemically induced* / Q000503:physiopathology*; D051381:Rats; D020303:Rats, Inbred Dahl / Q000502:physiology*; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000804:Angiotensin II; D012083:Renin; D000109:Acetylcholine