Patel K P, Zeigler D W
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68148-4575.
Proc Soc Exp Biol Med. 1993 Jan;202(1):81-7. doi: 10.3181/00379727-202-43515.
To determine whether renal nerves are involved in natriuresis or diuresis produced by the intracerebroventricular administration of clonidine (0.2, 2.0, and 8 micrograms/kg/min, and 2.0 microliters/min), urine flow, and sodium excretion were measured before and during clonidine administration from innervated and contralateral denervated kidneys in anesthetized (Inactin, 0.1 g/kg, ip) Sprague-Dawley rats. Baseline urine flow and sodium excretion were elevated after renal denervation prior to infusion of clonidine. Examining urine flow and sodium excretion before and during clonidine infusion indicated significant increases in urine flow and sodium excretion from the innervated kidneys but not from the denervated kidneys, possibly due to the renal sympatho-inhibition in the innervated kidney. However, the higher doses of clonidine (2 and 8 micrograms/kg/min) may have diffused out of the intracerebroventricular space into the peripheral circulation and produced their effect by a direct action on the kidney. Subsequently, two experiments were performed to distinguish between a central action and peripheral action. First, clonidine was administered centrally with concurrent administration of an alpha 2-blocker, yohimbine (8 micrograms/kg/min, i.v.), peripherally. In a second experiment the dose of clonidine was reduced 10-fold such that this reduced dose did not produce a peripheral action but still produced the renal responses to central administration. The results of the latter two studies further confirmed that natriuresis and diuresis produced by intracerebroventricular administration of clonidine is in part mediated by renal nerves.
为了确定肾神经是否参与可乐定(0.2、2.0和8微克/千克/分钟,以及2.0微升/分钟)脑室内给药所产生的利钠或利尿作用,在麻醉(腹腔注射0.1克/千克英纳克)的Sprague-Dawley大鼠中,测量了可乐定给药前及给药期间来自有神经支配和对侧去神经支配肾脏的尿流量和钠排泄量。在输注可乐定之前,肾去神经支配后基线尿流量和钠排泄量升高。检查可乐定输注前及输注期间的尿流量和钠排泄量表明,有神经支配肾脏的尿流量和钠排泄量显著增加,而去神经支配的肾脏则不然,这可能是由于有神经支配肾脏的肾交感神经抑制作用。然而,较高剂量的可乐定(2和8微克/千克/分钟)可能已从脑室内空间扩散到外周循环,并通过对肾脏的直接作用产生其效应。随后,进行了两项实验以区分中枢作用和外周作用。首先,在中枢给予可乐定的同时,外周给予α2受体阻滞剂育亨宾(8微克/千克/分钟,静脉注射)。在第二项实验中,将可乐定的剂量降低10倍,使得这种降低后的剂量不会产生外周作用,但仍能产生对中枢给药的肾脏反应。后两项研究的结果进一步证实,脑室内给予可乐定所产生的利钠和利尿作用部分是由肾神经介导的。