These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway.

Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate ␤-amyloid (A␤). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential -3 fatty acid related to reduced AD risk and reduced A␤ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase A␤ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.

This study determined whether or not oxidative stress and vascular dysfunction in fructose-induced hyperinsulinemic rats are associated with activation of the vascular renin-angiotensin system (RAS). Four groups of rats were used. CONT rats were fed normal rat chow, CONT + CAP were fed normal rat chow and given 500 mg/L captopril in their drinking water, fructose-fed rats (FFR) were fed a high-fructose diet and

SUMMARY This study examines factors modulating blood pressure reduction in obese patients undergoing weight reduction on a low calorie protein diet. Plasma norepinephrine (NE) was correlated (r = 0.65, p < 0.01) with blood pressure in 20 obese patients prior to weight loss. Reductions in blood pressure levels following upright posture and isometric handgrip exercise were related to reduction in NE levels after these maneuvers. While plasma epinephrine levels declined in parallel with NE levels, plasma dopamine actually increased (p < 0.05) during the first 2 weeks of caloric restriction. Prior to weight loss the obese patients demonstrated a significant rise in prolactin levels following posture and exercise, but following caloric restriction this was not observed. Levels of plasma renin activity (PRA) and aldosterone obtained after posture and exercise maneuvers were reduced after 8 weeks of caloric restriction, and reductions in PRA were related to reductions in NE (r = 0.56, p < 0.01). Reductions in blood pressure in association with caloric restriction in these obese patients seems to result, in part, from reduced sympathetic nervous system activity as well as secondary effects of reduced adrenergic activity on renal sodium excretion and the renin-angiotensinaldosterone axis. (Hypertension 4: 686-691, 1982) KEY WORDS • obesity • blood pressure • catecholamines