title: Defective adrenergic responses in patients with arsenic-induced peripheral vascular disease.
abstract: Blackfoot disease is an endemic arsenic-induced peripheral vascular disease in southern Taiwan. The main pathologic feature is atherosclerosis, which may relate to imbalances of the adrenergic system. The purpose of this study is to investigate the peripheral adrenergic responses of patients with blackfoot disease. Eight patients with blackfoot disease and four age-matched healthy controls were enrolled in this study. Baseline cutaneous perfusion was measured with a laser Doppler flowmeter. The response of alpha-adrenoceptors in the cutaneous microcirculation was assessed with laser Doppler flowmetry with iontophoresis of phenylephrine into the nailfold. In vitro binding with (125)I-cyanopindolol determined beta-adrenoceptor density in lymphocytes. The cyclic adenosine monophosphate (cAMP) level at baseline and after isoproterenol stimulation reflects lymphocyte beta-adrenergic responsiveness. Results revealed persistently decreased skin perfusion in patients with blackfoot disease. In contrast, there was a transient decrease in skin perfusion in healthy controls after iontophoresis of phenylephrine. Both beta-2 receptor density and isoproterenol-stimulated cAMP levels in lymphocytes decreased. Increased peripheral alpha-adrenergic response and decreased beta-2-adrenergic response are related to increased vascular tone and result in atherosclerosis. Our findings of accentuated alpha-adrenergic response in microcirculation and decreased lymphocyte beta-2-adrenoceptor response play an important role in the pathogenesis of atherosclerosis in blackfoot disease.
authors.affiliation: Department of Dermatology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Lee
authors.forename: Huoy-Rou
authors.initials: HR
authors.lastname: Chang
authors.forename: Jau-Shiuh
authors.initials: JS
authors.lastname: Chen
authors.forename: Gwo-Shing
authors.initials: GS
authors.lastname: Chen
authors.forename: Hsin-Su
authors.initials: HS
authors.lastname: Yu
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D020261:Arsenic Poisoning / Q000150:complications* / Q000453:epidemiology; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007478:Iontophoresis; D007545:Isoproterenol / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D007866:Leg / Q000098:blood supply*; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology*; D011941:Receptors, Adrenergic / Q000187:drug effects*; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D014874:Water Pollutants, Chemical / Q000506:poisoning*; D014881:Water Supply
chemical_list: D000318:Adrenergic beta-Agonists; D011941:Receptors, Adrenergic; D014874:Water Pollutants, Chemical; D000242:Cyclic AMP; D007545:Isoproterenol