中性内肽酶对血管活性肠肽血浆和组织浓度的影响。

Effect of neutral endopeptidase on plasma and tissue concentrations of vaso-active intestinal peptide.

Duggan K A, Jones D M, Davis R E, Macdonald G J

Department of Medicine, Prince Henry Hospital, Sydney, New South Wales, Australia.

Clin Exp Pharmacol Physiol. 1994 Apr;21(4):307-9. doi: 10.1111/j.1440-1681.1994.tb02517.x.

Abstract

This study sought to determine if neutral endopeptidase metabolizes vaso-active intestinal peptide (VIP) and whether changes in the activity of this enzyme might explain the change in VIP metabolism which follows gastric sodium loading. The study also investigated whether prolonged inhibition of neutral endopeptidase was associated with inhibition of further secretion of VIP. 2. Male Sprague-Dawley rats were given the neutral endopeptidase inhibitor UK77,568 (10 mg/kg), or vehicle, tail vein injected, once or daily for 4 days. Two hours after injection the rats were anaesthetized, blood sampled to determine plasma concentrations of VIP and the hearts were harvested. Plasma and tissue concentrations of VIP were determined by radio-immunoassay. 3. Plasma VIP increased in response to UK77,568 at day 1 (P < 0.0005) but did not differ from control at day 4. The concentration of VIP in the heart did not increase at day 1 but had increased significantly at day 4 (P < 0.01). 4. It was concluded that neutral endopeptidase may metabolize VIP. Further, the increased concentration of VIP in the heart and the return of its plasma concentration to control levels at day 4 may be consistent with suppression of continued VIP secretion.

摘要

本研究旨在确定中性内肽酶是否代谢血管活性肠肽（VIP），以及该酶活性的变化是否可以解释胃钠负荷后VIP代谢的变化。该研究还调查了长期抑制中性内肽酶是否与抑制VIP的进一步分泌有关。2. 给雄性斯普拉格-道利大鼠尾静脉注射中性内肽酶抑制剂UK77,568（10毫克/千克）或赋形剂，注射一次或每日注射4天。注射后两小时，将大鼠麻醉，采集血液以测定血浆中VIP的浓度，并摘取心脏。通过放射免疫测定法测定血浆和组织中VIP的浓度。3. 第1天，血浆VIP因UK77,568而升高（P<0.0005），但第4天与对照组无差异。心脏中VIP的浓度在第1天没有增加，但在第4天显著增加（P<0.01）。4. 得出的结论是，中性内肽酶可能代谢VIP。此外，第4天心脏中VIP浓度增加，而其血浆浓度恢复到对照水平，这可能与持续的VIP分泌受到抑制一致。