Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats
Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats
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DOI：
10.1152/ajprenal.1999.276.5.f767
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发表时间：
1999-05-01
影响因子：
4.2
通讯作者：
Danielson, LA
中科院分区：
文献类型：
--
作者：
Conrad, KP;Gandley, RE;Danielson, LA
妊娠早期肾脏和其他非生殖器官血管显著扩张。由于一氧化氮（NO）被发现介导清醒妊娠大鼠肾血管舒张和高滤过，而内源性内皮素（ET）被认为是在非妊娠大鼠的肾循环血管舒张，我们测试是否内皮素介导的NO依赖性变化在妊娠期间的肾循环。在30 μ g/min RES-701-1（一种选择性ETB受体亚型拮抗剂）输注前和输注期间，在清醒的妊娠和未孕大鼠中测量肾小球滤过率（GFR）和有效肾血浆流量（ERPF）。妊娠大鼠的基线GFR和ERPF相对于未孕对照组显著增加35%。在输注RES-701-1期间，妊娠大鼠的反应更强烈，显示GFR和ERPF均出现更大程度的下降，使得两组大鼠的肾功能趋于一致。在输注SB-209760（一种非选择性ETA/B受体亚型拮抗剂）期间，ERPF也在妊娠和未孕大鼠中聚集。联合输注N-ω-硝基-L-精氨酸甲酯[L-NAME，一种NO合酶（NOS）抑制剂]和RES-701-1可将GFR和ERPF降低至与单独给予任一药物所达到的水平相当的水平，表明抑制了常见的血管舒张途径。RES-701-1和SB-209670显着降低cGMP含量的小肾动脉从妊娠和处女大鼠在体外，加强肾内皮ETB受体亚型和NO之间的联系。重要的是，我们表明，RES-701-1是不是一个直接抑制剂的NOS。我们的结论是，内皮素介导的NO依赖性的变化，在清醒的大鼠在怀孕期间的肾循环。
Profound vasodilation of the kidneys and other nonreproductive organs transpires during early pregnancy. Because nitric oxide (NO) was found to mediate renal vasodilation and hyperfiltration in conscious pregnant rats, and endogenous endothelin (ET) was suggested to be vasodilatory in the renal circulation of nonpregnant rats, we tested whether endothelin mediates the NO dependent changes in the renal circulation during pregnancy. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in conscious pregnant and virgin rats before and during infusion of 30 mu g/min RES-701-1 (a selective ETB receptor subtype antagonist). Baseline GFR and ERPF were significantly increased by 35% in gravid rats relative to virgin controls. During infusion of RES-701-1, the pregnant rats responded more robustly, showing a greater decline in both GFR and ERPF such that renal function converged in the two groups of rats. ERPF also converged in pregnant and virgin rats during infusion of SB-209760, a nonselective ETA/B receptor subtype antagonist. Combined infusion of N-omega-nitro-L-arginine methyl ester [L-NAME, an NO synthase (NOS) inhibitor] and RES-701-1 reduced GFR and ERPF to levels comparable to those reached with either agent given alone, suggesting inhibition of a common vasodilatory pathway. RES-701-1 and SB-209670 significantly lowered the cGMP content of small renal arteries from gravid and virgin rats in vitro, strengthening the link between the renal endothelial ETB receptor subtype and NO. Importantly, we showed that RES-701-1 is not a direct inhibitor of NOS. We conclude that endothelin mediates the NO-dependent changes in the renal circulation of conscious rats during pregnancy.