Key result
Combination therapy with olmesartan and renal denervation significantly decreased systolic blood pressure, sympathetic nerve activity, and plasma aldosterone in hypertensive mice with CKD.
Why the study?
Does olmesartan combined with renal denervation reduce blood pressure and sympathetic nerve activity in hypertensive mice with chronic kidney disease?
Does olmesartan combined with renal denervation reduce blood pressure and sympathetic nerve activity in hypertensive mice with chronic kidney disease?
Combination therapy with olmesartan and renal denervation reduces blood pressure, sympathetic nerve activity, and plasma aldosterone in a mouse model of hypertension and chronic kidney disease.
BACKGROUND: Augmented sympathetic nerve activity (SNA) and renin-angiotensin-aldosterone system (RAAS) activity are involved in the pathogenesis of hypertension (HT) accompanied by chronic kidney disease (CKD). Oxidative stress in the hypothalamus increases SNA in HT. Administration of an angiotensin ΙΙ receptor blocker (olmesartan; OLM) or renal denervation (RDN) exerts an antihypertensive effect in HT with CKD; however, the precise mechanisms of the combination therapy are not fully elucidated. In the present study, we examined whether combination therapy with OLM and RDN reduces both SNA by decreasing oxidative stress in the hypothalamus and RAAS activity in hypertensive mice with CKD. METHODS AND RESULTS: In 5/6-nephrectomized ICR-mice (Nx-mice) at 4-weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by increased SNA and albuminuria compared with control-mice. Nx-mice were orally administered OLM, vehicle, or underwent RDN during OLM administration, and divided into Nx-OLM, Nx-VEH, and Nx-OLM/RDN groups, respectively. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH at 8-weeks after treatment, SBP was significantly decreased and both SNA and oxidative stress levels in the hypothalamus were significantly suppressed, without worsened creatinine clearance. In Nx-OLM and Nx-OLM/RDN compared with Nx-VEH, albuminuria was also suppressed, and the heart per body weight was decreased. In Nx-OLM/RDN, but not in Nx-OLM, the plasma aldosterone concentration was significantly decreased compared with Nx-VEH. CONCLUSION: These findings suggest that combination therapy with OLM/RDN has antihypertensive effects in association with suppressing SNA by reducing oxidative stress in the hypothalamus and the plasma aldosterone concentration in hypertensive mice with CKD.
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Nishihara et al. (2018) studied Hypertension with chronic kidney disease. Olmesartan combined with renal denervation vs. Vehicle or olmesartan alone was evaluated on Systolic blood pressure, sympathetic nerve activity, oxidative stress, and plasma aldosterone concentration. Combination therapy with olmesartan and renal denervation significantly decreased systolic blood pressure, sympathetic nerve activity, and plasma aldosterone in hypertensive mice with CKD.
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