Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics in two-kidney Goldblatt hypertension.
Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics in two-kidney Goldblatt hypertension.
复制标题
加压素和血管紧张素 II 对双肾 Goldblatt 高血压肾微循环动力学改变的相对贡献。
DOI：
10.1161/01.res.53.5.592
复制
发表时间：
1983
影响因子：
20.1
通讯作者：
Brenner,BM
中科院分区：
文献类型：
--
作者：
Ichikawa,I;Ferrone,RA;Duchin,KL;Manning,M;Dzau,VJ;Brenner,BM
研究了23只双肾单夹Goldblatt高血压大鼠未夹肾时肾脏微循环的变化。放置肾动脉夹4周后，高血压大鼠平均全身动脉压为163 +/- 5 mm Hg，而假手术对照组为108 +/- 2 mm Hg （n = 6只大鼠）。未夹肾的高血压大鼠肾小球毛细血管水压升高，单肾元肾小球滤过率升高，传入小动脉阻力增大。高血压大鼠肾小球毛细血管超滤系数明显降低。在其中10只大鼠中，静脉输注血管紧张素拮抗剂saralasin或转换酶抑制剂SQ20881，导致全身动脉压和传入和输出小动脉阻力显著降低，平均分别降低8 +/- 3%，15 +/- 4%和28 +/- 5%。这些变化与肾小球血浆流量显著增加有关，而超滤系数未受影响。在saralasin或SQ20881存在的情况下，输注精氨酸血管加压素血管作用的特异性拮抗剂导致明显的全身血管舒张，而不是肾脏血管舒张。因此，尽管全身动脉压进一步下降，平均下降23 +/- 2%，但肾小动脉阻力保持不变，导致肾小球毛细血管水压（下降18 +/- 2%）和肾小球血浆流速（下降28 +/- 10%）显著降低。由于抗利尿激素拮抗剂引起的肾小球压力和流量的显著降低，尽管超滤系数正常化，但高血压大鼠的单肾单位肾小球滤过率仍显著下降（34.6% +/- 6%）。当高血压大鼠（n = 7）单独使用抗利尿激素拮抗剂治疗时，在肾小动脉抵抗没有改变的情况下，再次观察到全身动脉压的适度下降。由于抗利尿激素拮抗剂的这种选择性肾外血管扩张作用，肾小球毛细血管水压、血浆流速和单肾元肾小球滤过率再次显著下降。当这些抗利尿素拮抗剂预处理的高血压大鼠给予saralasin或SQ20881时，观察到肾小动脉阻力显著降低，肾小球血浆流速显著增加。在急性抑制血管紧张素II和血管加压素的过程中观察到，这两种激素可能在高血压大鼠维持全身性高血压中起重要作用。由于加压素对肾外血管而非肾内血管的优先收缩作用，可维持Goldblatt高血压大鼠非剪切肾的高肾小球压力和血流。
The renal microcirculation was assessed in non-clipped kidneys of 23 Munich-Wistar rats with two-kidney one-clip Goldblatt hypertension. Four weeks after placement of a renal arterial clip, mean systemic arterial pressure averaged 163 +/- 5 mm Hg in hypertensive rats as compared to 108 +/- 2 in sham-operated controls (n = 6 rats). Non-clipped kidneys in hypertensive rats were characterized by higher glomerular capillary hydraulic pressures, single nephron glomerular filtration rate, and afferent arteriolar resistance. The glomerular capillary ultrafiltration coefficient was significantly reduced in hypertensive rats. In 10 of these rats, intravenous infusion of the angiotensin antagonist, saralasin, or the converting enzyme inhibitor, SQ20881, led to significant reductions in systemic arterial pressure and in afferent and efferent arteriolar resistance, on average by 8 +/- 3%, 15 +/- 4%, 28 +/- 5%, respectively. These changes were associated with significant increase in glomerular plasma flow, while ultrafiltration coefficient remained unaffected. In the presence of saralasin or SQ20881, infusion of a specific antagonist of the vascular action of arginine vasopressin led to significant systemic but not renal vasodilation. Thus, whereas systemic arterial pressure fell further, on average by 23 +/- 2%, renal arteriolar resistance remained constant, resulting in marked reduction in glomerular capillary hydraulic pressures (by 18 +/- 2%) and glomerular plasma flow rate (by 28 +/- 10%). Because of these pronounced reductions in glomerular pressures and flows induced by vasopressin antagonist, single nephron glomerular filtration rate fell markedly in hypertensive rats (by 34 +/- 6%) despite normalization of ultrafiltration coefficient. When hypertensive rats (n = 7) were treated with vasopressin antagonist alone, a modest fall in systemic arterial pressure was again observed in the absence of changes in renal arteriolar resistance. Due to this selective extrarenal vasodilatory action of vasopressin antagonist, glomerular capillary hydraulic pressure, plasma flow rate, and single nephron glomerular filtration rate again fell markedly. When these vasopressin antagonist pre-treated hypertensive rats were given saralasin or SQ20881, marked reductions in renal arteriolar resistance were observed in association with a significant increase in glomerular plasma flow rate. These observations made during acute inhibition of angiotensin II and vasopressin indicate that both of these vasopressin hormones may play important roles in maintaining systemic hypertension in hypertensive rat. By virtue of its preferential constrictor effects on extrarenal rather than renal vasculature vasopressin serves to maintain high glomerular pressures and flows in the non-clipped kidney of Goldblatt hypertensive rats.