title: Pathogenesis of calcineurin inhibitor-induced hypertension.
abstract: This article reviews the current understanding of the mechanisms of calcineurin inhibitor-induced hypertension. Already early after the introduction of cyclosporine in the 1980s, vasoconstriction, sympathetic excitation and sodium retention by the kidney had been shown to play a role in this form of hypertension. The vasoconstrictive effects of calcineurin inhibitors are related to interference with the balance of vasoactive substances, including endothelin and nitric oxide. Until recently, the renal site of the sodium-retaining effect of calcineurin inhibitors was unknown. We and others have shown that calcineurin inhibitors increase the activity of the thiazide-sensitive sodium chloride cotransporter through an effect on the kinases WNK and SPAK. Here, we review the pertinent literature on the hypertensinogenic effects of calcineurin inhibitors, including neural, vascular and renal effects, and we propose an integrated model of calcineurin inhibitor-induced hypertension.
authors.affiliation: Department of Internal Medicine-Nephrology, Erasmus Medical Center, Rotterdam, The Netherlands. ejhoorn@gmail.com
authors.forename: Ewout J
authors.initials: EJ
authors.lastname: Hoorn
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Walsh
authors.forename: James A
authors.initials: JA
authors.lastname: McCormick
authors.forename: Robert
authors.initials: R
authors.lastname: Zietse
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Unwin
authors.forename: David H
authors.initials: DH
authors.lastname: Ellison
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D065095:Calcineurin Inhibitors; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D049992:Sodium Chloride Symporters / Q000187:drug effects / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D049992:Sodium Chloride Symporters; D012964:Sodium