Effect of age on high-fat diet-induced hypertension.

Aging and obesity both have a significant impact on central blood pressure (BP) regulation, and previous studies indicated that changes in central redox signaling with age may affect high-fat (HF) diet-induced cardiovascular responses. Therefore, we investigated the effects of 60% HF feeding on BP regulation in young adult (5 mo) and old (26 mo) Fischer-344 × Brown-Norway rats. Radiotelemetric transmitters were implanted to measure BP, heart rate (HR), locomotor activity, and spontaneous baroreflex sensitivity. Expression and activity of NADPH oxidase and ANG II type 1 receptor were assessed in the hypothalamus and in the nucleus tractus solitarii. Old animals gained more weight on HF diet compared with young, whereas central NADPH oxidase expression and activity elevated similarly in the two age groups. After an initial hypotensive and tachycardic response during the first week of HF feeding, BP in young animals increased and became significantly elevated after 6 wk of HF feeding. In contrast, BP in old animals remained depressed. Nighttime HR and locomotor activity decreased in both young and old rats fed with HF diet, but these changes were more significant in young rats. As a result, amplitudes of circadian variation of BP, HR, and activity that were originally higher in young rats declined significantly and became similar in the two age groups. In conclusion, our experiments led to the surprising finding that HF diet has a more serious impact on cardiovascular regulation in young animals compared with old.

Hypertensive effects of central angiotensin II infusion and restraint stress are reduced with age.

OBJECTIVE: We investigated the effect of age on cardiovascular responses mediated by central angiotensin II (AngII) after intracerebroventricular infusion of AngII, and during restraint stress. METHODS: Blood pressure (BP) and heart rate (HR) of young (5-month-old) and old (27-month-old) male Fischer-344 x Brown-Norway rats were measured using radiotelemetry. AngII was infused intracerebroventricularly using osmotic minipumps (10 ng/0.5 microl/h for 11 days). BP and HR responses to stress were evaluated by placing animals in restrainers for 20 min before and after intracerebroventricular infusion of the AngII-type-1 receptor inhibitor losartan (15 microg/microl per h for 3 days). RESULTS: Resting BP was significantly elevated and HR was significantly lower in old rats compared with young. AngII-induced BP increase was markedly reduced in old rats, but HR responses were similar. Diurnal variation of both BP and HR was lower in old animals, and AngII reduced the amplitude of BP variation in young rats, but not in old. Restraint stress-induced BP and HR elevations were reduced with age. BP responses were diminished by central losartan infusion in both young and old, but this effect was more significant in young rats. In addition, expression of CuZn-superoxide dismutase and catalase declined significantly with age in the hypothalamus, whereas baseline oxidative stress increased. In contrast, AngII-induced increase in hypothalamic oxidative stress decreased with age. CONCLUSION: This study demonstrates that the role of central AngII diminishes with age in the regulation of BP both during baseline conditions and during stress, whereas the involvement of AngII in the regulation of HR remains unaffected.