Fasting recovers age-related hypertension in the rats: reset of renal renin-angiotensin system components and klotho

The renal renin-angiotensin system (RAS) plays a vital part in the control of blood pressure and is known to be affected by aging. This study aimed to investigate the effects of intermittent fasting on age-related hypertension and the expression of local renal RAS components.

The Wistar rats were categorized into three main age groups (young, middle aged, and elderly) and three dietary treatment models, including ad libitum feeding (AL), every other day fasting (EOD), and one day per week of fasting (FW). After three months, blood pressure (BP) was assessed. Some genes and proteins of the renal RAS system were measured by using Real time PCR and Western blot. α-klotho and Ang II proteins were assessed by ELISA method.

Old rats exhibited significantly increase in BP and Ang II (P < 0.001 vs. young rats) and a significant reduction in circulating levels of α-klotho and kidney AT2R protein (P < 0.001, P < 0.01, vs. young rats, respectively). Additionally, they respond to aging by increasing the AT1aR/AT2R proteins ratio (P < 0.05). Two model of feeding reduced BP in old rats and circulating Ang II in middle-aged and older rats. Moreover, by fasting, ACE2 protein expression was elevated in old rats. EOD fasting also significantly elevated the AT2 receptor protein and reduced the AT1aR/AT2R proteins ratio in the older rats (P < 0.001, P < 0.01, respectively).

Our findings suggest that fasting, particularly EOD, can attenuate age-related hypertension, partly through reset of the local renal RAS and increase of klotho protein expression.