Pace-Asciak C R, Carrara M C, Rangaraj G, Nicolaou K C
Prostaglandins. 1978 Jun;15(6):1005-12. doi: 10.1016/0090-6980(78)90043-6.
Intact rings and homogenates of aorta from spontaneously hypertensive rats (SHR) contain enhanced capacity over normal rats (NR) to convert arachidonic acid into PGI2. The PGI2 synthetic system in SHR is stimulated to a greater extent than NR by norepinephrine. Indomethacin blocks this stimulation. PGE2 and PGF2alpha were detected in much smaller amounts in homogenates (undetected in rings) but their formation was not enhanced by the hypertensive tissue. The identity of PGI2 was based on 1) direct pharmacological assay on the rat blood pressure. In this system identical vasodepressor responses to PGI2 are observed after intracarotid and intrajugular administration 2) indirectly as 6-keto PGF1alpha isolated after incubation of aortic homogenates with tritiated arachidonic acid and 3) indirectly by GC-MS assay of PGE2, PGF2alpha and 6-keto PGF1alpha formed during incubation of aortic homogenates with excess unlabeled arachidonic acid. These results provide additional support to our recent hypothesis that PGI2, of aortic origin, might actively participate in the regulation of systemic blood pressure. Its enhanced formation by intact hypertensive vascular tissue reflects an increase in the number of enzyme molecules immediately available to the substrate. This could probably be an adaptive response to the elevated levels of catecholamines in the circulation.
自发性高血压大鼠（SHR）主动脉的完整环和匀浆相较于正常大鼠（NR），将花生四烯酸转化为前列环素（PGI2）的能力增强。与NR相比，去甲肾上腺素对SHR中PGI2合成系统的刺激作用更强。吲哚美辛可阻断这种刺激。在匀浆中检测到的前列腺素E2（PGE2）和前列腺素F2α（PGF2α）含量少得多（在主动脉环中未检测到），但高血压组织并未增强它们的生成。PGI2的鉴定基于以下几点：1）对大鼠血压进行直接药理学测定。在该系统中，经颈动脉和颈静脉给药后，观察到对PGI2的相同降压反应；2）间接鉴定，即在用氚标记的花生四烯酸孵育主动脉匀浆后分离出6-酮-前列腺素F1α（6-keto PGF1α）；3）间接通过气相色谱-质谱法（GC-MS）测定在用过量未标记的花生四烯酸孵育主动脉匀浆过程中形成的PGE2、PGF2α和6-keto PGF1α。这些结果为我们最近的假说提供了更多支持，即源自主动脉的PGI2可能积极参与全身血压的调节。完整的高血压血管组织中其生成增加反映了可立即作用于底物的酶分子数量增加。这可能是对循环中儿茶酚胺水平升高的一种适应性反应。
