Flückiger J P, Waeber B, Mimran A, Nussberger J, Wahba W K, Brunner H R
Division of Hypertension, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
J Cardiovasc Pharmacol. 1988;12 Suppl 3:S36-42.
Experiments were performed to compare the diuretic and natriuretic response to a moderate saline load between 12-week-old conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) male rats. The animals were infused intravenously with 0.9% NaCl, first for a 1-h equilibration period, at a rate of 20 microliters/min, then for a 2-h salt-loading phase at 40 microliters/min, and finally during a 1-h recovery at 20 microliters/min. Cumulative renal excretion of water and sodium was similar in SHR and WKY rats. In contrast, urinary kallikrein excretion (amidolytic assay) during the saline-expansion and recovery phases was significantly higher in SHR than in WKY rats. At the end of the salt-loading phase, plasma levels of atrial natriuretic peptide (ANP) were higher in SHR than in WKY rats (p less than 0.05). This was also true in animals infused with 5% dextrose instead of 0.9% NaCl. Splanchnic nerve activity remained stable throughout the study in SHR as well as in WKY rats. These data therefore indicate that SHR excrete water and sodium similarly to WKY rats when they are subjected to a moderate sodium load. Neither ANP nor the sympathetic nervous system seems to be directly implicated in the renal response to the moderate saline expansion. Whether the enhanced urinary kallikrein excretion observed in SHR reflects an active participation of the renal kallikrein-kinin system in their sodium handling remains uncertain.
进行实验以比较12周龄清醒自发性高血压大鼠(SHR)和正常血压的Wistar-Kyoto(WKY)雄性大鼠对中等盐负荷的利尿和利钠反应。给动物静脉输注0.9%氯化钠,首先以20微升/分钟的速率输注1小时进行平衡期,然后以40微升/分钟的速率进行2小时的盐负荷期,最后以20微升/分钟的速率进行1小时的恢复期。SHR和WKY大鼠的水和钠的累积肾排泄量相似。相反,在盐水扩容期和恢复期,SHR的尿激肽释放酶排泄量(酰胺水解测定)显著高于WKY大鼠。在盐负荷期结束时,SHR的血浆心房利钠肽(ANP)水平高于WKY大鼠(p<0.05)。在输注5%葡萄糖而非0.9%氯化钠的动物中也是如此。在整个研究过程中,SHR和WKY大鼠的内脏神经活动均保持稳定。因此,这些数据表明,SHR在承受中等钠负荷时,其水和钠的排泄与WKY大鼠相似。ANP和交感神经系统似乎均未直接参与对中等盐水扩容的肾反应。在SHR中观察到的尿激肽释放酶排泄增加是否反映了肾激肽释放酶-激肽系统在其钠处理中的积极参与仍不确定。