Amelioration By Tempol Of The Hypertensive And Baroreflex Depressant Effects Of Cyclosporine In Conscious Rats: Role Of Cardiac Autonomic Control

Abstract

Previous studies including ours showed that cyclosporine (CSA) causes hypertension and baroreflex dysfunction. This study tested the hypothesis that increased oxidative damage mediates CSA effects. Experiments were undertaken in rats to investigate the effects of individual and combined 7‐day treatments with CSA (25 mg/kg/day) and tempol (superoxide dismutase mimetic, 100 mg/kg/day) on BP, reflex HR responses to peripherally mediated pressor and depressor responses, and biomarkers of oxidative stress. The role of cardiac autonomic control in cyclosporine‐tempol interaction was also investigated. CSA elevates blood pressure and reduced reflex bradycardic (phenylephrine) and tachycardic (sodium nitroptrusside) responses. The ability of muscarinic (atropine) or β‐adrenoceptors (propranolol) blockade to reduce reflex HR responses was reduced in CSA‐treated rats, suggesting impairment by CSA of cardiac autonomic control. Concurrent administration of tempol abolished CSA‐induced hypertension, baroreflex dysfunction, and autonomic impairment. Tempol also reversed the CSA‐induced increases in aortic and brainstem nitrite/nitrate and malondialdehyde and decreases in aortic superoxide dismutase. These findings implicate oxidative stress, at peripheral and central sites, in CSA‐induced hypertension and baroreflex dysfunction.