Falardeau P, Robillard M, Martineau A
Prostaglandins. 1985 Apr;29(4):621-8. doi: 10.1016/0090-6980(85)90085-1.
The urinary levels of 2,3-dinor-6-oxo-PGF1 alpha (PGI2-M), a major metabolite of PGI2, are determined by the balance between the amount of PGI2 synthesized and the extent of its further metabolic oxidation. The purpose of the present study was to determine if the urinary excretion of PGI2-M can be used as a reliable index of the in vivo production of PGI2 in both normal Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). This involved the exclusion of differences in metabolism between these two strains of rats. In order to do so, we monitored the urinary excretion of PGI2-M during paired intravenous infusions of 6-oxo-PGF1 alpha (the stable product of the spontaneous hydrolysis of PGI2) in conscious, unrestrained SHR and WKY rats aged 12-15 weeks, in doses ranging from 250 to 700 ng. In one experiment, PGI2 was infused instead of 6-oxo-PGF1 alpha. The results of these experiments indicate that SHR and WKY rats are equal with regard to the transformation of 6-oxo-PGF1 alpha and PGI2 into PGI2-M. For both groups, there is a good correlation between the amount of 6-oxo-PGF1 alpha infused and the amount of PGI2-M excreted in urine. These observations confirm the validity of using the urinary levels of 2,3-dinor-6-oxo-PGF1 alpha as an index of PGI2 production in both WKY and SHR. In addition, they support the conclusions drawn from our previous studies, namely that SHR do not produce more PGI2 than WKY rats in vivo, contrary to the situation prevailing in vitro.
前列环素(PGI2)的主要代谢产物2,3-二去甲-6-氧代-PGF1α(PGI2-M)的尿排泄水平,由PGI2合成量与其进一步代谢氧化程度之间的平衡所决定。本研究的目的是确定PGI2-M的尿排泄是否可作为正常Wistar-Kyoto(WKY)大鼠和自发性高血压大鼠(SHR)体内PGI2生成的可靠指标。这涉及排除这两种品系大鼠之间代谢差异的影响。为实现此目的,我们监测了12至15周龄清醒、未束缚的SHR和WKY大鼠在静脉内成对输注6-氧代-PGF1α(PGI2自发水解的稳定产物)期间PGI2-M的尿排泄情况,输注剂量范围为250至700 ng。在一项实验中,输注的是PGI2而非6-氧代-PGF1α。这些实验结果表明,在将6-氧代-PGF1α和PGI2转化为PGI2-M方面,SHR和WKY大鼠并无差异。对于两组而言,输注的6-氧代-PGF1α量与尿中排泄的PGI2-M量之间存在良好的相关性。这些观察结果证实了将2,3-二去甲-6-氧代-PGF1α的尿排泄水平用作WKY和SHR中PGI2生成指标的有效性。此外,这些结果支持了我们先前研究得出的结论,即与体外情况相反,SHR在体内产生的PGI2并不比WKY大鼠多。