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.

Benidipine, a Long-Acting Calcium Channel Blocker, Inhibits Oxidative Stress in Polymorphonuclear Cells in Patients with Essential Hypertension

“…This may be partly explained by a decrease in systolic or diastolic arterial pressure. It has been reported that arterial pressure increases oxidative stress in vitro (14) and that ROS formation by PMNs is increased in spontaneously hypertensive rats (15,16) and in patients with essential hypertension (17). A significant relationship between blood pressure and ROS formation by PMNs has been observed in apparently healthy subjects (13), and more clearly in patients with essential hypertension (Fig.…”

Beraprost sodium, a prostacyclin (PGI2) analogue, ameliorates concanavalin A‐induced liver injury in mice

“…at a dose of 100 μg/kg in a volume of 0.1 ml, immediately after injection of Con A. The dose of 100 μg/kg was selected according to previous reports in several rat models showing that this dose is non‐toxic (11, 31). Preliminary experiments employing control rats confirmed that beraprost had no significant side effects, including liver damage, at this dose.…”

On Some Aspects of the Thermodynamic of Membrane Recycling Mediated by Fluid Phase Endocytosis: Evaluation of Published Data and Perspectives

“…In animal model of spontaneous hypertension, neutrophils are activated and degranulate spontaneously [11] and this is directly associated with cardiovascular pathology [12]. Kristal et al [57] have reported increased superoxide release in the blood of essential hypertension patients compared with normotensive controls and neutrophil activation occurs in patients with unstable angina pectoris and acute myocardial infarction [58][59][60].…”

“…In recent years, the physiological importance of endocytosis and exocytosis has been highlighted in several pathologies such as Down syndrome (DS) [6], pre-Alzheimer's disease (AD) [6], cancer [7], multi drug resistance [8][9][10] and hypertension-mediated inflammation [11,12].…”