The Effects of Angiotensin II or Angiotensin 1-7 on Rat Pial Microcirculation during Hypoperfusion and Reperfusion Injury: Role of Redox Stress.

Renin-angiotensin systems produce angiotensin II (Ang II) and angiotensin 1-7 (Ang 1-7), which are able to induce opposite effects on circulation. This study in vivo assessed the effects induced by Ang II or Ang 1-7 on rat pial microcirculation during hypoperfusion-reperfusion, clarifying the mechanisms causing the imbalance between Ang II and Ang 1-7. The fluorescence microscopy was used to quantify the microvascular parameters. Hypoperfusion and reperfusion caused vasoconstriction, disruption of blood-brain barrier, reduction of capillary perfusion and an increase in reactive oxygen species production. Rats treated with Ang II showed exacerbated microvascular damage with stronger vasoconstriction compared to hypoperfused rats, a further increase in leakage, higher decrease in capillary perfusion and marker oxidative stress. Candesartan cilexetil (specific Ang II type 1 receptor (AT1R) antagonist) administration prior to Ang II prevented the effects induced by Ang II, blunting the hypoperfusion-reperfusion injury. Ang 1-7 or ACE2 activator administration, preserved the pial microcirculation from hypoperfusion-reperfusion damage. These effects of Ang 1-7 were blunted by a Mas (Mas oncogene-encoded protein) receptor antagonist, while Ang II type 2 receptor antagonists did not affect Ang 1-7-induced changes. In conclusion, Ang II and Ang 1-7 triggered different mechanisms through AT1R or MAS receptors able to affect cerebral microvascular injury.

Effects of intentional weight loss on physical and cognitive function in middle-aged and older obese participants: a pilot study.

OBJECTIVES: Obesity is a risk factor for cognitive decline and dementia. Whether weight loss improves cognition in older obese adults is not known. The objective was to investigate the effects of intentional weight loss on physical and cognitive function in middle-aged and older obese adults attending a weight loss clinic. METHOD: Eleven male and 39 female nonsmoking, adult obese (body mass index 30-50 kg/m(2)) participants were recruited. Participants were stratified by age: middle aged (30-59 years) and older aged (≥ 60 years). The weight loss target for each subject was 8% to 12% of initial body weight. Information on anthropometry, bioelectrical impedance, hand-grip strength, Mini-Mental State Examination (MMSE), Short Portable Mental Status Questionnaire (SPMSQ), and Trail-Making Test (TMT) A and B were collected at baseline and after weight loss. RESULTS: At baseline, older participants showed a nonsignificant trend for lower global cognitive function (MMSE, SPMSQ) and significantly slower processing speed (TMT-A). Twenty-one participants completed the weight loss study. The average weight loss relative to baseline was 9.7% ± 2.1%. Weight loss was associated with significant improvements in hand-grip strength and cognitive function (MMSE, TMT-A, and TMT-B). MMSE scores improved significantly only in older obese participants (p < 0.05). CONCLUSIONS: Weight loss in middle-aged and in older obese participants has a beneficial effect on cognitive and physical function. If confirmed in future trials, weight loss can significantly affect public health strategies for the prevention of dementia as well as on the clinical management of obesity.