Vågnes Øyvind B, Iversen Bjarne M, Arendshorst William J
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Am J Physiol Renal Physiol. 2007 Sep;293(3):F860-7. doi: 10.1152/ajprenal.00510.2006. Epub 2007 Jun 13.
The relative contributions of vasoconstrictor and of dilator systems are balanced in health. The balance is reset in disease, often favoring a predominant role of vasoconstrictors, perhaps due to positive interactions between constrictor systems. For example, in hypertension, chronic high levels of angiotensin II (ANG II) stimulate the production of thromboxane (TxA2/PGH2) and/or isoprostane that activate constrictor thromboxane prostanoid (TP) receptors in the vasculature. The present study evaluated a modest concentration of ANG II administered acutely into the renal artery on urinary excretion of TxB2 and isoprostane and possible renal TP receptor activation that might amplify ANG II-induced renal vasoconstriction. TP receptors were blocked with SQ29548 coinfused with ANG II. Results were compared with a time control group of continuous ANG II infusion (40 ng.min(-1).kg body wt(-1)) over 90 min. TP receptor antagonism during 30-60 min had no effect on the reduction in renal blood flow (RBF) produced by ANG II (15.8 +/- 2.8 vs. 13.2 +/- 4.9%) (P > 0.6). Likewise, there was no difference between groups during ANG II-induced renal vasoconstriction between 60-90 min in presence or absence of TP receptor antagonist (RBF -8.6 +/- 4.0 vs. -9.6 +/- 4.5%) (P > 0.8). Systemic arterial pressure was stable throughout, so RBF changes reflected localized changes in renal vascular resistance. Urinary excretion of TxB2 and isoprostane were nearly doubled by ANG II. The present data indicate that short-term intrarenal infusion of ANG II rapidly increases renal production of TxA2 but that the ANG II-induced renal vasoconstriction is independent of TP receptor activation during the initial 90 min of local challenge with ANG II.
在健康状态下，血管收缩系统和舒张系统的相对作用是平衡的。在疾病状态下，这种平衡会被重新调整，血管收缩系统往往占据主导地位，这可能是由于收缩系统之间的正性相互作用所致。例如，在高血压中，慢性高水平的血管紧张素II（ANG II）刺激血栓素（TxA2/PGH2）和/或异前列腺素的产生，这些物质可激活血管系统中的收缩性血栓素前列腺素（TP）受体。本研究评估了急性注入肾动脉的适量ANG II对TxB2和异前列腺素尿排泄的影响，以及可能导致的肾TP受体激活，这种激活可能会放大ANG II诱导的肾血管收缩。TP受体用与ANG II共同输注的SQ29548阻断。将结果与90分钟内持续输注ANG II（40 ng·min⁻¹·kg体重⁻¹）的时间对照组进行比较。在30 - 60分钟内进行TP受体拮抗对ANG II引起的肾血流量（RBF）减少没有影响（15.8 ± 2.8%对13.2 ± 4.9%）（P > 0.6）。同样，在60 - 90分钟内，无论有无TP受体拮抗剂，ANG II诱导的肾血管收缩组间均无差异（RBF -8.6 ± 4.0%对 -9.6 ± 4.5%）（P > 0.8）。整个过程中全身动脉压稳定，因此RBF变化反映了肾血管阻力的局部变化。ANG II使TxB2和异前列腺素的尿排泄量几乎增加了一倍。目前的数据表明，短期肾内输注ANG II可迅速增加肾TxA2的产生，但在局部给予ANG II的最初90分钟内，ANG II诱导的肾血管收缩与TP受体激活无关。
