McKeogh Donogh F, O'Donaughy Theresa L, Brooks Virginia L
Department of Internal Medicine, Oregon Health & Science University, Portland, OR 97239, USA.
Am J Physiol Heart Circ Physiol. 2004 Apr;286(4):H1258-65. doi: 10.1152/ajpheart.00791.2003. Epub 2003 Dec 4.
Nitric oxide (NO) appears to inhibit sympathetic tone in anesthetized rats. However, whether NO tonically inhibits sympathetic outflow, or whether endogenous angiotensin II (ANG II) promotes NO-mediated sympathoinhibition in conscious rats is unknown. To address these questions, we determined the effects of NO synthase (NOS) inhibition on renal sympathetic nerve activity (RSNA) and heart rate (HR) in conscious, unrestrained rats on normal (NS), high-(HS), and low-sodium (LS) diets, in the presence and absence of an ANG II receptor antagonist (AIIRA). When arterial pressure was kept at baseline with intravenous hydralazine, NOS inhibition with l-NAME (10 mg/kg i.v.) resulted in a profound decline in RSNA, to 42 +/- 11% of control (P < 0.01), in NS animals. This effect was not sustained, and RSNA returned to control levels by 45 min postinfusion. l-NAME also caused bradycardia, from 432 +/- 23 to 372 +/- 11 beats/min postinfusion (P < 0.01), an effect, which, in contrast, was sustained 60 min postdrug. The effects of NOS inhibition on RSNA and HR did not differ between NS, HS, and LS rats. However, when LS and HS rats were pretreated with AIIRA, the initial decrease in RSNA after l-NAME infusion was absent in the LS rats, while the response in the HS group was unchanged by AIIRA. These findings indicate that, in contrast to our hypotheses, NOS activity provides a stimulatory input to RSNA in conscious rats, and that in LS animals, but not HS animals, this sympathoexcitatory effect of NO is dependent on the action of endogenous ANG II.
一氧化氮（NO）似乎可抑制麻醉大鼠的交感神经张力。然而，NO是否持续抑制交感神经输出，或者内源性血管紧张素II（ANG II）是否促进清醒大鼠中NO介导的交感神经抑制作用尚不清楚。为了解决这些问题，我们在清醒、不受束缚的大鼠中，在给予和不给予ANG II受体拮抗剂（AIIRA）的情况下，测定了正常（NS）、高钠（HS）和低钠（LS）饮食条件下，一氧化氮合酶（NOS）抑制对肾交感神经活动（RSNA）和心率（HR）的影响。当通过静脉注射肼屈嗪使动脉压维持在基线水平时，在NS组动物中，用左旋精氨酸甲酯（l-NAME，10 mg/kg静脉注射）抑制NOS会导致RSNA显著下降，降至对照值的42±11%（P<0.01）。这种作用不能持续，输注后45分钟时RSNA恢复到对照水平。l-NAME还引起心动过缓，输注后心率从432±23次/分钟降至372±11次/分钟（P<0.01），相比之下，药物注射后60分钟该作用仍持续存在。NOS抑制对RSNA和HR的影响在NS、HS和LS大鼠之间没有差异。然而，当LS和HS大鼠用AIIRA预处理时，LS大鼠在l-NAME输注后最初的RSNA下降消失，而HS组的反应不受AIIRA影响。这些发现表明，与我们的假设相反，NOS活性为清醒大鼠的RSNA提供了刺激性输入，并且在LS动物而非HS动物中，NO的这种交感神经兴奋作用依赖于内源性ANG II的作用。
