• Anesthesia and analgesia · Dec 2005

    Inhibition of poly (ADP-ribose) synthetase improves pulmonary arterial endothelium-dependent relaxation after ischemic-reperfusion injury of splanchnic artery in rats.

    • Hirofumi Nagata, Takashi Horiguchi, Keiji Enzan, Toshiaki Nishikawa, and Kenji Suzuki.
    • Department of Anesthesia and Intensive Care, Akita University School of Medicine, Hondo 1-1-1, Akita City, Akita 010-8543, Japan.
    • Anesth. Analg. 2005 Dec 1;101(6):1799-804.

    AbstractThe role of poly (adenosine diphosphate-ribose) synthetase (PARS) in the contractile and relaxant responses of pulmonary arteries injured by ischemia and reperfusion (IR) of splanchnic artery has not been evaluated. We examined these responses by using 3-aminobenzamide, a pharmacological inhibitor of PARS. IR models in rats were induced by clamping the superior mesenteric artery for 60 min, followed by release of the clamp for 60 min. In the 2 treated groups, 5 or 10 mg/kg of 3-aminobenzamide was administered as an IV bolus at 10 min before reperfusion, followed by infusion rates of 5 and 10 mg.kg(-1).h(-1), respectively, during the period of reperfusion (IR + PARS inhibitor 5 and 10 groups). In the vehicle-treated group, 3-aminobenzamide was not given, but IV saline was administered (IR group). In the control group, surgery was performed, but the superior mesenteric artery was not occluded (sham group). The pulmonary arteries were isolated, and effects of drugs were evaluated in vitro. The IR group showed no attenuation of the contractile responses of the pulmonary artery to phenylephrine. The relaxant responses to endothelium-dependent vasodilators, acetylcholine, and A23187 in the IR group were significantly inhibited when compared with the sham group. The reduction in the relaxant response to endothelium-dependent vasodilators was improved in the IR + PARS inhibitor 5 and 10 groups when compared with the IR group. We concluded that IR attenuated the relaxant responses of the pulmonary artery to endothelium-dependent vasodilators and that PARS inhibitors ameliorate the reduction in the relaxant response.

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