Enhanced neutrophil superoxide anion production and its modification by beraprost sodium in spontaneously hypertensive rats

To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneou sly hypertensive rats (SHR) and the effect of beraprost sodium (BS) on thes e functions, we examined superoxide anion (O-2-) production and adherent ac tivity 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 Wist ar-Kyoto (WKY) rats. In study 2 (ex vivo), 14-week-old SHR received vehicle (n = 6) and BS (30 mug/kg/day [n = 6] and 100 mug/kg/day [n = 71]) once da ily for 4 weeks. In study 3 (in vitro), PMN from 18-week-old SHR were incub ated with BS (0.1 and 1 mu mol/L) and theophylline (200 mu mol/L), which is reported to inhibit the PMN O-2- production. Systolic blood pressure, plat elet counts, and PMN O-2- production stimulated by phorbol eater myristate acetate were significantly elevated in 4-week-old SHR compared with WKY (P < .05). Beraprost sodium decreased the ex vivo PMN O-2- production, serum s uperoxide dismutase activity, and platelet counts (P < .05); however, BS di d not reduce the in vitro PMN O-2- production. These data support our hypot hesis that the enhanced PMN function contributes to the cardiovascular dama ges during the early phase of SHR, and that BS:has merit for preventing the O-2- related organ damages in this model. (C) 2001 American Journal of Hyp ertension, Ltd.