Christiansen R E, Roald A B, Gjerstad C, Tenstad O, Iversen B M
Renal Research Group, Institute of Medicine, University of Bergen, Norway.
Kidney Blood Press Res. 2001;24(3):176-84. doi: 10.1159/000054225.
BACKGROUND/AIMS: To gain insight into the effect of arginine vasopressin (AVP) on renal hemodynamics in hypertensive rats, we investigated the vasoconstrictive response to AVP on total renal blood flow (RBF) and total and zonal glomerular filtration rate (GFR) in young and old spontaneously hypertensive rats (SHR). A hypothesis of increased AVP sensitivity in the juxtamedullary cortex of SHR was tested.
Total RBF and total and zonal GFR were studied in 10- and 40-week-old SHR and normotensive Wistar-Kyoto rats (WKY). RBF was recorded by a flowmeter before infusion of AVP and immediately after injection of a bolus dose of 10 ng AVP. Whole kidney GFR and its intracortical distribution was measured by the tubular uptake of 125I- and 131I-labelled aprotinin before and during a continuous infusion of AVP 5 ng/min. Ligand binding measurements of preglomerular V1a receptors were performed in young and old rats.
RBF decreased by 43 +/- 3% in 10-week SHR (9.2 +/- 0.5 vs. 5.2 +/- 0.3 ml x min(-1) x g(-1)), significantly more than 10-week WKY where RBF decreased by 35 +/- 3% (9.6 +/- 0.7 vs. 6.5 +/- 0.5 ml x min(-1) x g(-1)) (p < 0.05). The effect of AVP on RBF was attenuated in 40-week-old rats where the decline in RBF was 29 +/- 5% in SHR and 23 +/- 4% in WKY (p > 0.05). GFR decreased by 6 +/- 3% (1.03 +/- 0.04 vs. 0.96 +/- 0.04 ml x min(-1) x g(-1), p < 0.05) in 10-week SHR and was unchanged in 10-week WKY (1.10 +/- 0.07 vs. 1.08 +/- 0.04 ml x min(-1) x g(-1), p > 0.10). GFR decreased by 11 +/- 10% in 40-week SHR and by 4 +/- 4% in 40-week WKY (p > 0.05). AVP infusion significantly increased filtration fraction in all groups except 40-week SHR, indicating that AVP has the strongest vasoconstrictive effect on postglomerular vessels. The intrarenal distribution of GFR was unchanged in the normotensive and hypertensive groups. V1a receptor density was upregulated in young SHR compared to young WKY (p < 0.05), but downregulated in old compared to young SHR (p = 0.05).
The results indicate that AVP sensitivity is not increased in the juxtamedullary cortex in SHR and the reduced vasoconstrictive effect in old SHR is due to a reduced density of V1a receptors.
背景/目的：为深入了解精氨酸加压素（AVP）对高血压大鼠肾血流动力学的影响，我们研究了年轻和老年自发性高血压大鼠（SHR）对AVP的血管收缩反应对总肾血流量（RBF）以及总肾小球滤过率和分区肾小球滤过率（GFR）的影响。对SHR髓质旁皮质中AVP敏感性增加的假说进行了验证。
在10周龄和40周龄的SHR以及血压正常的Wistar-Kyoto大鼠（WKY）中研究了总RBF以及总GFR和分区GFR。在输注AVP前和注射10 ng AVP大剂量推注后立即用流量计记录RBF。在以5 ng/min的速度持续输注AVP之前和期间，通过肾小管对125I和131I标记的抑肽酶的摄取来测量全肾GFR及其皮质内分布。对年轻和老年大鼠进行肾小体前V1a受体的配体结合测量。
10周龄SHR的RBF下降了43±3%（9.2±0.5对5.2±0.3 ml·min-1·g-1），显著高于10周龄WKY，后者RBF下降了约35±3%（9.6±0.7对6.5±0.5 ml·min-1·g-1）（p<0.05）。在40周龄大鼠中，AVP对RBF的影响减弱，SHR中RBF下降29±5%，WKY中下降23±4%（p>0.05）。10周龄SHR的GFR下降了6±3%（1.03±0.04对0.96±0.04 ml·min-1·g-1，p<0.05），而在WKY中无变化（1.10±0.07对1.08±0.04 ml·min-1·g-1，p>0.10）。40周龄SHR的GFR下降了11±10%，40周龄WKY下降了4±4%（p>0.05）。除40周龄SHR外，AVP输注在所有组中均显著增加滤过分数，表明AVP对肾小球后血管具有最强的血管收缩作用。在血压正常和高血压组中，GFR的肾内分布没有变化。与年轻WKY相比，年轻SHR中V1a受体密度上调（p<0.05），但与年轻SHR相比，老年SHR中V1a受体密度下调（p=？此处原文可能有误，推测为p = 0.05）。
结果表明，SHR髓质旁皮质中AVP敏感性并未增加，老年SHR中血管收缩作用减弱是由于V1a受体密度降低。
