Abstract:Objective To investigate the effects of losartan (an angiotensin receptor blocker[ARB]) combined with spironolactone (an aldosterone receptor antagonist) on basilar artery and cognitive functions of elderly spontaneous hypertension rats (SHR). Methods Eighteen elderly male SHR rats were evenly randomized into SHR group (SHR control group), L group (losartan 20 mg/[kg·d]), and L+S group (losartan 20 mg/[kg·d]and spironolactone 10 mg/[kg·d]at the same time); six age-matched male Wistar Kyoto (WKY) rats with normal blood pressure served as controls (WKY group). Drug intervention lasted for 4 weeks by gavage after 4 weeks of adaptation. The blood pressure of rats in each group was measured by noninvasive tail-cuff method. Spatial memory ability was tested by Y-maze, and systolic and diastolic functions of rat basilar artery were tested with isolated vascular rings. Results The systolic blood pressure (SBP) of rats in SHR group was significantly higher than that in WKY group, while the SBP of rats in L group and L+S group was significantly lower than that in SHR group, with more significant decline in L+S group (all P<0.05). In the Y-maze test, no significant difference was found in spontaneous alternation rates between SHR group and WKY group (P>0.05). The spontaneous alternation rate of L group was significantly lower than that of SHR group (P<0.05). The spontaneous alternation rate of L+S group was significantly lower than those of L group and WKY group (both P<0.05). The systolic response of rat basilar artery in SHR group was stronger than that in WKYgroup in a low-concentration KCl solution, while it was weakened in a high-concentration KCl solution; losartan alone could enhance the systolic response of basilar artery, but the combined use of losartan and spironolactone could significantly reduce the systolic response. Conclusion ARBs combined with aldosterone receptor antagonists can effectively control blood pressure, but adverse effects may appear on the cognitive function of elderly SHR if the blood pressure becomes too low.