Mechanism of cyclosporine-induced sympathetic activation and acute hypertension in rats

Abstract

Although intravenous cyclosporine A (CsA) previously has been shown to cause a robust sympathetically mediated increase in blood pressure in the rat, the underlying mechanism by which CsA increases the activity of the sympathetic nervous system is unknown. To determine the relative contributions of central neural versus peripheral reflex mechanisms in causing this sympathetic activation, we recorded efferent renal sympathetic nerve activity and blood pressure during intracerebroventricular or intravenous infusion of CsA, the latter performed in intact rats and in those with sinoaortic denervation, cervical or subdiaphragmatic vagotomy, or dorsal rhizotomy (T10 through L1). In intact rats, intravenous CsA (5 mg/kg), as expected, tripled renal sympathetic nerve activity and increased mean arterial pressure by 27±4 mm Hg (P