Lohmeier T E, Reinhart G A, Mizelle H L, Han M, Dean M M
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Am J Physiol. 1998 Oct;275(4):R1239-46. doi: 10.1152/ajpregu.1998.275.4.R1239.
To determine whether the chronically denervated kidney is supersensitive to either physiological or pathophysiological plasma levels of norepinephrine (NE), studies were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated and innervated kidneys. Plasma NE concentration was increased by chronic infusion of NE (4-5 days) at rates of 25, 100, and 200 ng . kg-1 . min-1. Twenty-four-hour control values for mean arterial pressure (MAP), plasma NE concentration, and ratios for urinary sodium and potassium excretion from denervated and innervated kidneys (Den/Inn) were 94 +/- 4 mmHg, 145 +/- 24 pg/ml, 1.05 +/- 0.05, and 0.97 +/- 0.07, respectively. With infusions of NE producing plasma levels of NE of up to approximately 3,000 pg/ml or plasma concentrations of NE at least threefold greater than present under most pathophysiological conditions and during acute activation of the sympathetic nervous system, there were no significant long-term changes in MAP or relative excretion rates of sodium and potassium from denervated and innervated kidneys. In marked contrast, pharmacological plasma levels of NE ( approximately 7,000 pg/ml) produced chronic increases in MAP (to 116 +/- 2% of control) and sustained reductions in Den/Inn for urinary sodium and potassium excretion to 57 +/- 4 and 68 +/- 5% of control, respectively, indicating a lower excretion rate of these electrolytes from denervated vs. innervated kidneys. We conclude that the chronically denervated kidney does not exhibit an exaggerated antinatriuretic response to either physiological or pathophysiological levels of circulating NE. It is therefore unlikely that renal denervation supersensitivity is a confounding issue in studies employing chronic renal denervation to elucidate the role of the renal nerves in the regulation of sodium excretion.
为了确定长期去神经支配的肾脏是否对生理或病理生理水平的去甲肾上腺素（NE）超敏感，研究人员对清醒犬进行了实验。这些犬接受了单侧肾脏去神经支配，并将膀胱手术分为两个半膀胱，以便分别收集去神经支配和有神经支配的肾脏的24小时尿液。通过以25、100和200 ng·kg⁻¹·min⁻¹的速率慢性输注NE（4 - 5天）来提高血浆NE浓度。去神经支配和有神经支配的肾脏的平均动脉压（MAP）、血浆NE浓度以及尿钠和钾排泄率比值（Den/Inn）的24小时对照值分别为94±4 mmHg、145±24 pg/ml、1.05±0.05和0.97±0.07。在输注NE使血浆NE水平高达约3000 pg/ml或血浆NE浓度至少比大多数病理生理条件下和交感神经系统急性激活时高出三倍的情况下，MAP以及去神经支配和有神经支配的肾脏的钠和钾相对排泄率没有显著的长期变化。与之形成鲜明对比的是，药理学水平的NE（约7000 pg/ml）使MAP长期升高（达到对照值的116±2%），并使尿钠和钾排泄的Den/Inn持续降低，分别降至对照值的57±4%和68±5%，这表明去神经支配的肾脏相对于有神经支配的肾脏，这些电解质的排泄率更低。我们得出结论，长期去神经支配的肾脏对循环中生理或病理生理水平的NE不会表现出过度的利钠反应减弱。因此，在采用慢性肾脏去神经支配来阐明肾神经在钠排泄调节中的作用的研究中，肾去神经支配超敏感性不太可能是一个混杂问题。
