title: Cyclosporine impairs vasodilation without increased sympathetic activity in humans.
abstract: Hypertension and nephrotoxicity frequently complicate treatment with cyclosporine; two suggested mechanisms are increased sympathetic activity and altered vascular reactivity. It is difficult to assess these mechanisms in patients receiving cyclosporine after transplantation because of the accompanying major physiological alterations. Therefore, we studied 12 patients with rheumatoid arthritis twice--while they were taking and not taking cyclosporine. We measured vascular response in the dorsal hand vein using the linear variable differential transformer technique. Cyclosporine treatment significantly attenuated vasodilation induced by 60 ng/min isoproterenol (no cyclosporine, 19.8 +/- 3.5% versus cyclosporine, 7.9 +/- 2.2%; P = .02) and prostaglandin E1 at 1000 pg/min (no cyclosporine, 72.6 +/- 10.2% versus cyclosporine 45.6 +/- 9.0%) and 2000 pg/min (no cyclosporine, 100.8 +/- 14.7% versus cyclosporine, 68.6 +/- 8.0%; F = 5.47, P = .047). However, neither vascular response to phenylephrine or nitroglycerin nor sympathetic activity assessed by measurement of norepinephrine spillover with a radioisotope dilution technique was affected by cyclosporine (no cyclosporine, 516.1 +/- 47.9 ng/min versus cyclosporine, 476.6 +/- 51.8 ng/min; P = .42). Cyclosporine impaired venodilation in response to two agonists that act through adenylate cyclase without altering alpha-agonist-induced venoconstriction or sympathetic activity. Therefore, in humans impaired vasodilation rather than sympathetic activation or enhanced vasoconstriction may be an important mechanism for the alterations of vascular tone that occur after long-term cyclosporine administration.
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tenn 37232-6602, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Stein
authors.forename: H
authors.initials: H
authors.lastname: He
authors.forename: T
authors.initials: T
authors.lastname: Pincus
authors.forename: A J
authors.initials: AJ
authors.lastname: Wood
mesh_terms: D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006225:Hand / Q000098:blood supply; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects*; D014680:Veins
chemical_list: D010656:Phenylephrine; D016572:Cyclosporine; D000527:Alprostadil; D007545:Isoproterenol