Abstract 11557: Combination Therapy of Amlodipine with Atorvastatin Suppresses Sympathetic Nerve Activity and Improves Cognitive Function Independent of Depressor Effects
Backgrounds: Amlodipine (AM) is a widely used anti-hypertensive agent, however, does not suppress the sympathetic nervous system (SNS). Previously we demonstrated that oral administration of atorvastatin (ST, statin) suppressed SNS, without depressor effect, through its anti-oxidant effect in the cardiovascular center (rostral ventrolateral medulla; RVLM) of the brainstem of hypertensive rats. Furthermore, numerous clinical and basic reports have suggested that both AM and ST improved cognitive function in hypertension. The aim of the present study was to determine whether the combination therapy of AM and ST suppresses SNS and improves cognitive function.
Methods and Results: We used stroke-prone spontaneously hypertensive rats (SHRSP) as a hypertensive model with sympathoexcitation. We put those rats on AM, AM+ST, ST or vehicle (CNT) for 28 days. After the treatment, AM and AM+ST lowered mean blood pressure to the similar levels (AM; 132±16mmHg, AM+ST; 128±12mmHg, ST; 158±9mmHg, CNT; 161±11mmHg, n=5 for each, p<0.01). Urinary norepinephrine excretion (uNE, an index of sympathoexcitation) was lower in ST or AM+ST than AM or CNT, but lowest in AM+ST (AM+ST; 1.1±0.1ug, ST; 1.4±0.2ug vs. AM; 2.0±0.2ug, CNT; 1.9±0.3ug, n=5 for each, p<0.01). Oxidative stress in the RVLM was significantly lower in ST than in AM or CNT, and was significantly lower in AM+ST than in ST (AM+ST; 0.5±0.1umol/g, ST; 0.7±0.1umol/g vs. AM; 1.1±0.2umol/g, CNT; 1.0±0.1umol/g, n=5 for each, p<0.01). Cognitive function determined by water maze test was significantly better in AM or ST than in CNT. Cognitive function was the best in AM+ST (AM+ST; 6±1sec, ST; 11±2sec, AM; 10±1sec vs. CNT; 19±3sec, n=5 for each, p<0.01).
Conclusion: Combination therapy of amlodipine with atorvastatin causes sympathoinhibition through their anti-oxidant effect in the RVLM and improves the cognitive function in hypertensive rats independent of the depressor effects.
- © 2011 by American Heart Association, Inc.