Li Yi-Fan, Mayhan William G, Patel Kaushik P
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha, NE 68198-4575, USA.
Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1738-46. doi: 10.1152/ajpheart.00727.2002.
Acute volume expansion (VE) produces a suppression of renal sympathetic nerve discharge (RSND) resulting in diuresis and natriuresis. Recently, we have demonstrated that the endogenous nitric oxide (NO) system within the paraventricular nucleus (PVN) produces a decrease in RSND. We hypothesized that endogenous NO in the PVN is involved in the suppression of RSND leading to diuretic and natriuretic responses to acute VE. To test this hypothesis, we first measured the VE-induced increase in renal sodium excretion and urine flow with and without blockade of NO, with microinjection of NG-monomethyl-L-arginine (L-NMMA; 200 pmol in 200 nl), within the PVN of Inactin-anesthetized male Sprague-Dawley rats. Acute VE produced significant increases in urine flow and sodium excretion, which were diminished in rats treated with L-NMMA within the PVN. This effect of NO blockade within the PVN on VE-induced diuresis and natriuresis was abolished by renal denervation. Consistent with these data, acute VE induced a decrease in RSND (52% of the baseline level), which was significantly blunted by prior administration of L-NMMA into the PVN (28% of the baseline level) induced by a comparable level of acute VE. Using the push-pull perfusion technique, we found that acute VE induced a significant increase in NOx concentration in the perfusate from the PVN region. Taken together, these results suggest that acute VE induces an increase in NO production within the PVN that leads to renal sympathoinhibition, resulting in diuresis and natriuresis. We conclude that NO within the PVN plays an important role in regulation of sodium and water excretions in the volume reflex via modulating renal sympathetic outflow.
急性容量扩张（VE）会抑制肾交感神经放电（RSND），从而导致利尿和利钠。最近，我们已经证明室旁核（PVN）内的内源性一氧化氮（NO）系统会使RSND减少。我们推测PVN中的内源性NO参与了对RSND的抑制，从而导致对急性VE的利尿和利钠反应。为了验证这一假设，我们首先在Inactin麻醉的雄性Sprague-Dawley大鼠的PVN内，通过微量注射NG-单甲基-L-精氨酸（L-NMMA；200 nl中含200 pmol），测量了在有无NO阻断情况下VE诱导的肾钠排泄和尿流量增加。急性VE使尿流量和钠排泄显著增加，而在PVN内用L-NMMA处理的大鼠中这些增加有所减少。肾去神经支配消除了PVN内NO阻断对VE诱导的利尿和利钠的这种作用。与这些数据一致，急性VE诱导RSND降低（降至基线水平的52%），而预先向PVN内注射L-NMMA可使这种降低显著减弱（降至基线水平的28%），此时急性VE的水平相当。使用推挽灌注技术，我们发现急性VE使PVN区域灌流液中的NOx浓度显著增加。综上所述，这些结果表明急性VE诱导PVN内NO生成增加，进而导致肾交感神经抑制，从而产生利尿和利钠作用。我们得出结论，PVN内的NO通过调节肾交感神经流出，在容量反射中钠和水排泄的调节中起重要作用。
