title: Enhanced neutrophil superoxide anion production and its modification by beraprost sodium in spontaneously hypertensive rats.
abstract: To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneously hypertensive rats (SHR) and the effect of beraprost sodium (BS) on these functions, we examined superoxide anion (O2-) production and adherent activity by PMN, as well as modification of these functions by BS ex vivo and in vitro. In study 1, we measured PMN functions in 4-week-old SHR and Wistar-Kyoto (WKY) rats. In study 2 (ex vivo), 14-week-old SHR received vehicle (n = 6) and BS (30 microg/kg/day [n = 6] and 100 microg/kg/day [n = 7]) once daily for 4 weeks. In study 3 (in vitro), PMN from 18-week-old SHR were incubated with BS (0.1 and 1 micromol/L) and theophylline (200 micromol/L), which is reported to inhibit the PMN O2- production. Systolic blood pressure, platelet counts, and PMN O2- production stimulated by phorbol ester myristate acetate were significantly elevated in 4-week-old SHR compared with WKY (P < .05). Beraprost sodium decreased the ex vivo PMN O2- production, serum superoxide dismutase activity, and platelet counts (P < .05); however, BS did not reduce the in vitro PMN O2- production. These data support our hypothesis that the enhanced PMN function contributes to the cardiovascular damages during the early phase of SHR, and that BS has merit for preventing the O2- related organ damages in this model.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohmori
authors.forename: Y
authors.initials: Y
authors.lastname: Kitoh
authors.forename: A
authors.initials: A
authors.lastname: Kawaguchi
authors.forename: K
authors.initials: K
authors.lastname: Harada
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006973:Hypertension / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D013481:Superoxides; C048081:beraprost; D011464:Epoprostenol