title: Central modulation of cyclosporine-induced hypertension.
abstract: Arterial hypertension is a considerable side effect that accompanies the clinical use of immunosuppressant drugs such as cyclosporine (CSA). In addition to promoting graft rejection, uncontrolled hypertension is a major risk factor for atherosclerosis, left ventricular hypertrophy, heart failure, and premature death. Most, if not all, reports that reviewed the hypertensive effect of CSA and underlying mechanisms focused on the roles of peripheral vasoactive machinaries, perhaps because of the limited capacity of CSA to diffuse to brain tissues and the lack of any appreciable effect for centrally administered CSA on blood pressure (BP) or central sympathetic outflow. This review focuses primarily on evidence that supports a modulatory role for central neural pathways, as go-between afferent and efferent sympathetic circuits, in the elicitation of the hypertensive action of CSA. Other areas covered briefly in the review include (1) an outline of peripheral mechanisms that contribute to the hypertensive action of CSA, and (2) comparisons of the BP effects of CSA and other calcineurin-dependent (tacrolimus) and independent (sirolimus) immunosuppressants. The knowledge of these mechanisms, central and peripheral, may permit the identification of new therapeutic strategies against CSA hypertension.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
authors.forename: Hanan M
authors.initials: HM
authors.lastname: El-Gowelli
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
mesh_terms: D000818:Animals; D065095:Calcineurin Inhibitors / Q000009:adverse effects*; D016572:Cyclosporine / Q000009:adverse effects*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine