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Enhanced neutrophil superoxide anion production and its modification by beraprost sodium in spontaneously
M Ohmori1, Y Kitoh, A Kawaguchi
1Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
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.
Insights
Enhanced polymorphonuclear leukocyte (PMN) function contributes to cardiovascular damage in spontaneously hypertensive rats (SHR). Beraprost sodium (BS) reduces PMN superoxide anion production ex vivo, suggesting a protective role against organ damage.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Immunology
Background:
- Polymorphonuclear leukocytes (PMN) play a role in cardiovascular damage.
- Spontaneously hypertensive rats (SHR) exhibit elevated PMN activity.
- The effect of beraprost sodium (BS) on PMN function in SHR requires clarification.
Purpose of the Study:
- To investigate PMN function, specifically superoxide anion (O2-) production and adherent activity, in SHR.
- To determine the effect of beraprost sodium (BS) on PMN functions ex vivo and in vitro.
- To assess the potential of BS in mitigating cardiovascular damage in SHR.
Main Methods:
- Compared PMN functions in young SHR and Wistar-Kyoto (WKY) rats.
- Administered BS to adult SHR for 4 weeks and measured PMN functions ex vivo.
- Incubated PMN from SHR with BS in vitro to assess direct effects.
Main Results:
- Elevated systolic blood pressure, platelet counts, and PMN O2- production in young SHR compared to WKY rats.
- BS treatment significantly decreased ex vivo PMN O2- production, serum superoxide dismutase activity, and platelet counts in SHR.
- BS did not inhibit PMN O2- production in vitro.
Conclusions:
- Enhanced PMN function contributes to cardiovascular damage in the early stages of hypertension in SHR.
- Beraprost sodium demonstrates potential in preventing O2- related organ damage in SHR by modulating PMN function ex vivo.
- Further research is warranted to elucidate the precise mechanisms of BS action on PMN in hypertensive models.
