Goto F, Jackson E K, Ohnishi A, Herzer W, Branch R A
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.
J Pharmacol Exp Ther. 1987 Dec;243(3):799-803.
The potential for endogenous prostaglandin production to modulate the renal vascular response to intrarenal infusions of angiotensin II (AII) was investigated in the canine kidney at varying renal perfusion pressures (RPP), using suprarenal aortic constriction to vary RPP. AII, infused to achieve increments in renal arterial plasma concentrations of 300 pg/ml, induced reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) when RPP was 80 mm Hg or above. When RPP was reduced to 60 mm Hg, AII decreased RBF, but GFR failed to change. The vasoconstrictor response to AII was enhanced by indomethacin (8 mg/kg) at all perfusion pressures, but was not modified by the thromboxane (Tx) A2 synthase inhibitor, UK 38,485 (1 mg/kg). In contrast, the lack of change in GFR in response to AII at a RPP of 60 mm Hg was converted to a significant reduction by both indomethacin and UK 38,485. These observations are consistent with the hypothesis that the effect of AII on RBF is attenuated by renal release of vasodilator prostaglandins at all RPP. However, at low RPP, AII infusion also induces the release a factor that increases GFR. As this response can be prevented by both TxA2 synthase and cyclooxygenase inhibition, it is possible that this factor is TxA2.
利用肾上主动脉缩窄来改变肾灌注压（RPP），研究了内源性前列腺素产生对犬肾肾血管对肾内输注血管紧张素II（AII）反应的调节作用。输注AII以使肾动脉血浆浓度增加300 pg/ml，当RPP为80 mmHg或更高时，可导致肾血流量（RBF）和肾小球滤过率（GFR）降低。当RPP降至60 mmHg时，AII使RBF降低，但GFR未改变。在所有灌注压下，吲哚美辛（8 mg/kg）均可增强对AII的血管收缩反应，但血栓素（Tx）A2合酶抑制剂UK 38,485（1 mg/kg）对其无影响。相反，在60 mmHg的RPP下，吲哚美辛和UK 38,485均使AII引起的GFR无变化转变为显著降低。这些观察结果与以下假设一致：在所有RPP下，肾释放的血管舒张性前列腺素减弱了AII对RBF的作用。然而，在低RPP时，输注AII还会诱导释放一种增加GFR的因子。由于这种反应可被TxA2合酶和环氧化酶抑制所阻止，因此该因子可能是TxA2。
