Progression and reversal of coronary and mesenteric vascular dysfunction associated with obesity.

Objective: The purpose of this study was to examine progression and reversal of microvascular complications when rats were fed a high fat diet.

Methods: Sprague-Dawley rats 10 weeks of age were fed a diet containing 45% kcal fat for up to 32 weeks. Blood pressure and heart rate was measured by telemetry. Vascular reactivity of aorta and small coronary and mesenteric vessels was determined after 8, 16, 24, and 32 weeks on diet.

Results: There was a modest increase in weight and blood pressure in high fat fed rats. Sodium nitroprusside (SNP)-induced relaxation of coronary arteries was potentiated after 8 weeks on high fat diet, however, this enhanced response was not observed after 16, 24, or 32 weeks of diet. Acetylcholine (Ach) mediated relaxation was attenuated after 16, 24, and 32 weeks of high fat diet in coronary arteries; however, in aorta and mesenteric arteries, Ach-mediated response was not altered until 32 weeks on high fat diet. Reversing the high fat diet for 8 weeks resulted in partial recovery of metabolic parameters; however endothelial function in coronary arteries remained impaired.

Conclusions: These studies indicate that high fat diet promotes progressive impairment of coronary vascular function that is difficult to reverse.