Diz D I, Baer P G, Nasjletti A
J Clin Invest. 1983 Aug;72(2):466-77. doi: 10.1172/jci110994.
We examined in rats the effects of intraperitoneal angiotensin II (AII) infusion for 12 d on urinary excretion, plasma concentration, and in vitro release of prostaglandin (PG) E2 and 6-keto-PGF1 alpha, a PGI2 metabolite. AII at 200 ng/min increased systolic blood pressure (SBP) progressively from 125 +/- 3 to 170 +/- 9 mmHg (P less than 0.01) and elevated fluid intake and urine volume. Urinary 6-keto-PGF1 alpha excretion increased from 38 +/- 6 to 55 +/- 5 and 51 +/- 7 ng/d (P less than 0.05) on days 8 and 11, respectively, of AII infusion, but urinary PGE2 excretion did not change. Relative to a control value of 129 +/- 12 pg/ml in vehicle-infused (V) rats, arterial plasma 6-keto-PGF1 alpha concentration increased by 133% (P less than 0.01) with AII infusion. Aortic rings from AII-infused rats released more 6-keto-PGF1 alpha (68 +/- 7 ng/mg) during 15-min incubation in Krebs solution than did rings from V rats (40 +/- 3 ng/mg); release of PGE2, which was less than 1% of that of 6-keto-PGF1 alpha, was also increased. Slices of inner renal medulla from AII-infused rats released more 6-keto-PGF1 alpha (14 +/- 1 ng/mg) during incubation than did slices from V rats (8 +/- 1 ng/mg, P less than 0.05), but PGE2 release was not altered. In contrast, AII infusion did not alter release of 6-keto-PGF1 alpha or PGE2 from inferior vena cava segments or from renal cortex slices. Infusion of AII at 125 ng/min also increased SBP, plasma 6-keto-PGF1 alpha concentration, and in vitro release of 6-keto-PGF1 alpha from rings of aorta and renal inner medulla slices; at 75 ng/min AII had no effect. SBP on AII infusion day 11 correlated positively with both 6-keto-PGF1 alpha plasma concentration (r = 0.54) and net aortic ring release (r = 0.70) when data from all rats were combined. We conclude that augmentation of PGI2 production is a feature of AII-induced hypertension. The enhancement of PGI2 production may be an expression of nonspecific alteration in vascular structure and metabolic functions during AII-induced hypertension, as well as the result of a specific effect of the peptide on the arachidonate-prostaglandin system.
我们研究了大鼠腹腔注射血管紧张素II（AII）12天对尿排泄、血浆浓度以及前列腺素（PG）E2和PGI2代谢产物6-酮-PGF1α体外释放的影响。以200 ng/min的速度注射AII使收缩压（SBP）从125±3 mmHg逐渐升高至170±9 mmHg（P<0.01），并增加了液体摄入量和尿量。在注射AII的第8天和第11天，尿中6-酮-PGF1α排泄量分别从38±6 ng/d增加至55±5 ng/d和51±7 ng/d（P<0.05），但尿中PGE2排泄量未改变。相对于注射赋形剂（V）的大鼠129±12 pg/ml的对照值，注射AII后动脉血浆6-酮-PGF1α浓度增加了133%（P<0.01）。在Krebs溶液中孵育15分钟期间，注射AII的大鼠的主动脉环释放的6-酮-PGF1α（68±7 ng/mg）比V大鼠的主动脉环（40±3 ng/mg）更多；PGE2的释放也增加，其释放量不到6-酮-PGF1α的1%。注射AII的大鼠的肾内髓质切片在孵育期间释放的6-酮-PGF1α（14±1 ng/mg）比V大鼠的切片（8±1 ng/mg，P<0.05）更多，但PGE2释放未改变。相比之下，注射AII并未改变下腔静脉段或肾皮质切片中6-酮-PGF1α或PGE2的释放。以125 ng/min的速度注射AII也增加了SBP、血浆6-酮-PGF1α浓度以及主动脉环和肾内髓质切片中6-酮-PGF1α的体外释放；以75 ng/min的速度注射AII则无作用。当合并所有大鼠的数据时，注射AII第11天的SBP与6-酮-PGF1α血浆浓度（r = 0.54）和主动脉环净释放量（r = 0.70）均呈正相关。我们得出结论，PGI2生成增加是AII诱导的高血压的一个特征。PGI2生成的增强可能是AII诱导的高血压期间血管结构和代谢功能非特异性改变的一种表现，也是该肽对花生四烯酸-前列腺素系统特定作用的结果。
