M. Ohmori et al., Enhanced neutrophil superoxide anion production and its modification by beraprost sodium in spontaneously hypertensive rats, AM J HYPERT, 14(7), 2001, pp. 722-728
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.