Holmer S, Rinne B, Eckardt K U, Le Hir M, Schricker K, Kaissling B, Riegger G, Kurtz A
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
Am J Physiol. 1994 May;266(5 Pt 2):F738-45. doi: 10.1152/ajprenal.1994.266.5.F738.
Utilizing a combination of mechanical and chemical unilateral denervation, we have examined the relevance of renal innervation for the expression of renin in kidneys of adult rats. Renal denervation led to a reduction by 57 +/- 4% of renin-containing areas in denervated kidneys as quantitated by morphometry of kidney sections immunoreactive against a polyclonal antirenin antibody. Preprorenin mRNA content in the denervated kidneys fell to 46 +/- 7% of the contralateral innervated kidneys. Treatment of rats with the beta 1-adrenoreceptor antagonist metoprolol (100 mg.kg-1.day-1) for 2 days decreased renal renin mRNA levels to 71% of control levels. Unilateral renal denervation led to a further decrease of renin mRNA levels also in metoprolol-treated animals to 60% of the values found in the contralateral kidneys. Hypotensive hemorrhage led to a 1.4-fold increase of renin mRNA in the kidneys of sham-treated animals. In unilaterally denervated rats renin mRNA increased to levels similar to those in sham-operated animals in both denervated and in contralateral innervated kidneys in response to bleeding. As a consequence, the ratio of abundance of renin mRNA in the denervated to the innervated kidneys rose to 86 +/- 7%. Pretreatment of the animals with metoprolol, on the other hand, prevented the rise of renin mRNA in response to hypotensive hemorrhage. Our findings suggest that in the adult organism renal neural input significantly contributes to the expression of renin under basal conditions, while it appears to be of less importance for stimulation of renin gene expression by severe blood loss.
利用机械和化学单侧去神经支配相结合的方法,我们研究了肾神经支配对成年大鼠肾脏中肾素表达的相关性。通过对用多克隆抗肾素抗体免疫反应的肾脏切片进行形态计量学分析,发现肾去神经支配导致去神经支配肾脏中含肾素区域减少57±4%。去神经支配肾脏中的前肾素mRNA含量降至对侧有神经支配肾脏的46±7%。用β1-肾上腺素能受体拮抗剂美托洛尔(100mg·kg-1·天-1)治疗大鼠2天,可使肾脏肾素mRNA水平降至对照水平的71%。单侧肾去神经支配也导致美托洛尔治疗动物的肾素mRNA水平进一步降低,降至对侧肾脏中发现值的60%。低血压性出血导致假手术动物肾脏中肾素mRNA增加1.4倍。在单侧去神经支配的大鼠中,去神经支配的肾脏和对侧有神经支配的肾脏中,肾素mRNA在出血后均增加到与假手术动物相似的水平。因此,去神经支配肾脏与有神经支配肾脏中肾素mRNA丰度之比升至86±7%。另一方面,用美托洛尔预处理动物可防止肾素mRNA因低血压性出血而升高。我们的研究结果表明,在成年机体中,肾神经输入在基础条件下对肾素的表达有显著贡献,而在严重失血刺激肾素基因表达方面似乎不太重要。