Atorvastatin Improves the Impaired Baroreflex Sensitivity via Anti-Oxidant Effect in the Rostral Ventrolateral Medulla of SHRSP

Abstract

We have demonstrated that oxidative stress in the rostral ventrolateral medulla (RVLM), a vasomotor center in brainstem, increases sympathetic nerve activity (SNA) and that oral administration of atorvastatin inhibited SNA via anti-oxidant effect in the RVLM of stroke-prone spontaneously hypertensive rats (SHRSPs). The impairment of baroreflex sensitivity (BRS) is known as the predictive factor of mortality in the hypertension and BRS is impaired in SHRSP. The aim of the present study was to determine whether oral administration of atorvastatin improved the impaired BRS via anti-oxidant effect in the RVLM in SHRSP. Atorvastatin (20 mg/kg/day) or vehicle was orally administered for 28 days in SHRSPs. Systolic blood pressure (SBP), heart rate, and 24-h urinary norepinephrine excretion as an indicator of SNA were comparable between atorvastatin- and control-SHRSP. Thiobarbituric acid-reactive substance (TBARS) levels as a marker of oxidative stress was significantly lower in atorvastatin-SHRSP than in control-SHRSP. Baroreflex sensitivity measured by the spontaneous sequence method was significantly higher in atorvastatin-SHRSP than in control-SHRSP. These results suggest that atorvastatin improves the impaired BRS in SHRSP via its anti-oxidant effect in the RVLM of SHRSP.

Keywords:

• statin
• oxidative stress
• brain
• hypertension
• baroreflex

Acknowledgments

We are grateful to Pfizer. USA, for supplying atorvastatin. This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (B19390231), and in part, by the Health and Labor Sciences Research Grant for Comprehensive Research in Aging and Health Labor and Welfare of Japan.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.