Azelnidipine inhibits the sympathetic nerve activity and improves baroreflex control of heart rate via anti‐oxidant effect in the rostral ventrolateral medulla

Abstract

Azelnidipine (AZL), a long‐acting dihydropyridine calcium channel blocker, is known to inhibit sympathetic nerve activity (SNA). We previously demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM) in the brainstem causes the sympathetic hyperactivity. The aim of this study was to determine whether AZL inhibits the SNA and improves the baroreflex sensitivity (BRS) via anti‐oxidant effect in the RVLM. AZL (20 mg/kg/day, n=5) or hydralazine (HYD; 20 mg/kg/day, n=5) was orally administered for 30 days in stroke‐prone spontaneously hypertensive rats (SHRSP). Thiobarbituric acid‐reactive substances (TBARS) levels in the RVLM were measured as a marker of oxidative stress. Reductions in SBP were similar between the two groups (−32±11mmHg vs −28±9mmHg, ns). HR increased significantly in HYD but did not change in AZL. Urinary norepinephrine excretion (UNE), measured as a marker of SNA, decreased significantly in AZL (−0.25±0.06μg, P<0.01), whereas increased significantly in HYD. BRS, measured by sequence method, was significantly improved in AZL to a great extent than in HYD (8±2ms/mmHg vs 4±2ms/mmHg, P<0.05). TBARS levels in the RVLM decreased significantly in AZL (−0.21±0.09 μmol/g wet wt, P<0.01) but not in HYD. In conclusion, azelnidipine inhibits the SNA and improves the BRS possibly via its anti‐oxidant effect in the RVLM.