Gross V, Lippoldt A, Bohlender J, Bader M, Hansson A, Luft F C
Franz Volhard Clinic, Humboldt University of Berlin, Germany.
J Am Soc Nephrol. 1998 Mar;9(3):346-54. doi: 10.1681/ASN.V93346.
The effect of acutely increasing renal perfusion pressure or extracellular fluid volume on renal medullary and cortical blood flow was examined in the low-renin deoxycorticosterone acetate (DOCA)-salt hypertension model in mice. A 50-mg DOCA tablet was implanted, and 1% saline was given as drinking water for 3 wk. Medullary and cortical blood flow were determined with laser-Doppler flowmetry, and whole-kidney blood flow was measured with a transit-time ultrasound flowprobe around the renal artery. In control mice, total renal blood flow ranged from 6.3 and 7.6 ml/min per g kidney weight and in DOCA-salt mice from 4.3 and 4.7 ml/min per g kidney weight, respectively, and was minimally affected as renal perfusion pressure was increased. Renal vascular resistance increased correspondingly. During stepwise increases in renal artery pressure from 90 to 140 mmHg, medullary blood flow progressively increased in control mice to 125% of baseline values, whereas cortical blood flow did not change. In DOCA-salt mice, increasing BP from 100 to 154 mmHg had no effect on either cortical or medullary blood flow. Urine flow and sodium excretion were lower in DOCA-salt mice than in controls and increased nearly to the same extent in both groups after volume expansion with isotonic saline. Total renal blood flow increased after saline loading, more in controls than in DOCA-salt mice. Increases in medullary blood flow after saline loading were up to 122% of baseline values in controls and demonstrated a significantly steeper slope than the 110% of baseline increases in DOCA-salt mice. Cortical blood flow, however, was not different between the groups. Thus, medullary blood flow is not as tightly autoregulated as cortical blood flow in normal mice. Natriuresis with acute volume loading is facilitated by increased medullary blood flow. In DOCA-salt mice, the medullary blood flow reaction to renal perfusion pressure increases is abolished, whereas flow increases with extracellular volume expansion are diminished. These results suggest that diminished pressure-natriuresis responses in DOCA-salt mice are related to perturbed medullary blood flow.
在低肾素醋酸脱氧皮质酮(DOCA)-盐高血压小鼠模型中,研究了急性增加肾灌注压或细胞外液量对肾髓质和皮质血流的影响。植入一片50 mg的DOCA片剂,并给予1%盐水作为饮用水,持续3周。用激光多普勒血流仪测定髓质和皮质血流,并用通过时间超声血流探头测量肾动脉周围的全肾血流。在对照小鼠中,总肾血流范围为每克肾重6.3至7.6 ml/min,在DOCA-盐小鼠中分别为每克肾重4.3至4.7 ml/min,并且随着肾灌注压的升高受到的影响最小。肾血管阻力相应增加。在肾动脉压力从90 mmHg逐步增加到140 mmHg的过程中,对照小鼠的髓质血流逐渐增加至基线值的125%,而皮质血流没有变化。在DOCA-盐小鼠中,将血压从100 mmHg提高到154 mmHg对皮质或髓质血流均无影响。DOCA-盐小鼠的尿流量和钠排泄低于对照小鼠,在用等渗盐水扩容后,两组的尿流量和钠排泄增加幅度几乎相同。盐水负荷后总肾血流增加,对照组比DOCA-盐小鼠增加更多。盐水负荷后,对照小鼠髓质血流增加至基线值的122%,并且其斜率明显比DOCA-盐小鼠基线增加的110%更陡。然而,两组之间的皮质血流没有差异。因此,在正常小鼠中,髓质血流的自身调节不像皮质血流那样严格。急性容量负荷引起的利钠作用通过髓质血流增加而促进。在DOCA-盐小鼠中,髓质血流对肾灌注压升高的反应被消除,而随着细胞外液量增加的血流增加则减弱。这些结果表明,DOCA-盐小鼠压力性利钠反应减弱与髓质血流紊乱有关。