Effect of age on high-fat diet-induced hypertension

Abstract

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.

Fig. 1.

Changes in caloric food intake (top) and body weight (bottom) of young and old animals fed with standard rat chow (C) or a 60% high-fat (HF) diet. Initially, all groups were fed with standard rat chow (between week −3 and 0). Next, from week 0, rats in HF groups were fed with a 60% HF diet. *Caloric food intake was significantly higher (P < 0.05) in old vs. young HF groups from the beginning of the study until day 17 of diet treatment. Body weight was significantly higher (P < 0.05) in old vs. young rats regardless of diet for the whole duration of the study. #P < 0.05 HF vs. age-matched controls.

Fig. 2.

Mean arterial blood pressure (MAP), heart rate (HR), and locomotor activity (ACT) measured during daytime (between 0600 and 1800 h, left) and nighttime (between 1800 and 0600 h, right) in young and old animals. Rats were fed standard rat chow between week −3 and 0 and a 60% HF diet beginning from week 0. AU, arbitrary units. *P < 0.05 young vs. old. †P < 0.05 HF feeding vs. baseline in young rats, indicates the first data point when HF effect became significant, except for HR and daytime ACT figures, where it indicates individual data points when values were significantly different from baseline. ‡P < 0.05 HF feeding vs. baseline in old animals, indicates the first data point when HF effect became significant, except for HR figures, where it indicates individual data points when values were significantly different from baseline.

Fig. 3.

A: relationship between daytime MAP and HR during the first 2 wk of HF feeding in young and old rats. Linear regression analysis indicated a slope of −2.25 in young rats (r² = 0.372, P < 0.01, broken line) and a slope of −2.7 in old animals (r² = 0.612, P < 0.01, solid line). B: relationship between nighttime locomotor activity and HR for the whole duration of the study in young and old rats. Linear regression analysis in young rats indicated a slope of 14.6 (r² = 0.872, P < 0.01, broken line). In contrast, correlation between locomotor activity and HR in old rats (solid line) was not significant.

Fig. 4.

Circadian variation of MAP, HR, and ACT in young and old animals fed with standard rat chow (left) and after 12 wk of HF diet feeding (right). *P < 0.05 young vs. old.

Fig. 5.

Spontaneous baroreflex sensitivity assessed in young and old rats fed with standard rat chow (control) and after HF diet feeding for 1 and 10 wk. *P < 0.05 young vs. old. #P < 0.05 HF vs. control.

Fig. 6.

mRNA levels of NADPH oxidase NOX-2 (A), p47 (B), and p67 (C) subunits and NADPH oxidase activity (D) in the hypothalamus of young and old rats fed with standard chow or HF diet. *P < 0.05 young vs. old. #P < 0.05 HF vs. control.