Oliver J A, Cannon P J
J Clin Invest. 1978 Mar;61(3):610-23. doi: 10.1172/JCI108972.
The mechanism whereby the vasoconstrictor response to angiotensin II (AII) is influenced by sodium balance or disease is unclear. To explore this question, the renal vascular responses (RVR) to intrarenal injections of subpressor doses of AII and norepinephrine were studied in dogs with an electromagnetic flowmeter. Acute and chronic sodium depletion increased plasma renin activity (PRA) and blunted the RVR to AII, while acute sodium repletion and chronic sodium excess plus desoxycorticosterone acetate decreased PRA and enhanced the RVR to AII. The magnitude of the RVR to AII was inversely related to PRA. The RVR to norepinephrine was unaffected by sodium balance and was not related to PRA. Inhibition of the conversion of angiotensin I to AII by SQ 20,881 during sodium depletion lowered mean arterial blood pressure (MABP), increased renal blood flow (RBF), and enhanced the RVR to AII but not to norepinephrine. Administration of bradykinin to chronically sodium-depleted dogs also lowered the MABP and increased RBF but had no effect on the RVR to AII. SQ 20,881 had no effect on MABP, RBF, or the RVR to AII in the dogs with chronic sodium excess and desoxycorticosterone acetate. Administration of indomethacin to chronically sodium-depleted dogs lowered RBF but did not influence the RVR to AII. The results indicate that the RVR to AII is selectively influenced by sodium balance and that the magnitude of the response is inversely related to the availability of endogenous AII. The data did not suggest that the variations in the RVR to AII were because of direct effects of sodium on vascular contraction, changes in the number of vascular AII receptors, or the renal prostaglandins. The results are consistent with the hypothesis that the vasoconstrictor effect of AII in the renal vasculature is primarily dependent upon the degree to which the AII vascular receptors are occupied by endogenous hormone.
血管紧张素II（AII）的血管收缩反应受钠平衡或疾病影响的机制尚不清楚。为探讨这一问题，使用电磁流量计对犬肾内注射低于升压剂量的AII和去甲肾上腺素后的肾血管反应（RVR）进行了研究。急性和慢性缺钠会增加血浆肾素活性（PRA），并减弱对AII的RVR，而急性补钠、慢性钠过量加醋酸脱氧皮质酮会降低PRA并增强对AII的RVR。对AII的RVR幅度与PRA呈负相关。对去甲肾上腺素的RVR不受钠平衡影响，且与PRA无关。在缺钠期间，SQ 20,881抑制血管紧张素I向AII的转化会降低平均动脉血压（MABP），增加肾血流量（RBF），并增强对AII而非去甲肾上腺素的RVR。给慢性缺钠犬注射缓激肽也会降低MABP并增加RBF，但对AII的RVR没有影响。SQ 20,881对慢性钠过量加醋酸脱氧皮质酮的犬的MABP、RBF或对AII的RVR没有影响。给慢性缺钠犬注射吲哚美辛会降低RBF，但不影响对AII的RVR。结果表明，对AII的RVR受钠平衡的选择性影响，且反应幅度与内源性AII的可用性呈负相关。数据并未表明对AII的RVR变化是由于钠对血管收缩的直接作用、血管AII受体数量的变化或肾前列腺素所致。这些结果与以下假设一致，即AII在肾血管系统中的血管收缩作用主要取决于AII血管受体被内源性激素占据的程度。
