Mattson D L, Bellehumeur T G
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Hypertension. 1996 Aug;28(2):297-303. doi: 10.1161/01.hyp.28.2.297.
We studied the effect of selective inhibition of the neural isoform of nitric oxide synthase in the rat renal medulla in conscious Sprague-Dawley rats. Continuous renal medullar interstitial infusion of an antisense oligonucleotide complementary to the initiation region of the mRNA for neural nitric oxide synthase increased blood pressure 14 +/- 1 mm Hg in rats maintained on a high sodium intake. Medullary interstitial infusion of saline vehicle or a scrambled oligonucleotide probe failed to alter blood pressure in separate groups of high salt control rats. Renal medullary interstitial infusion of the antisense oligonucleotide significantly decreased the level of neural nitric oxide synthase in the renal medulla by 53 +/- 8% and decreased total renal medullary nitric oxide synthase activity by 28 +/- 8%. No alterations were detected in the levels of inducible nitric oxide synthase or beta-actin in the antisense oligonucleotide-infused rats. To confirm the antisense oligonucleotide data, we administered a mechanistically different inhibitor of neural nitric oxide synthase, 7-nitroindazole, to an additional group of rats maintained on a high salt diet. Direct renal medullary interstitial infusion of this selective enzyme inhibitor significantly increased mean arterial pressure (15 +/- 6 mm Hg) and decreased total renal medullary nitric oxide synthase activity by 37 +/- 12% in rats on a high sodium diet. The present experiments demonstrate a role for the neural isoform of nitric oxide synthase in the long-term control of blood pressure in the presence of a high salt diet.
我们在清醒的Sprague-Dawley大鼠中研究了选择性抑制大鼠肾髓质中一氧化氮合酶神经亚型的作用。持续向肾髓质间质输注与神经型一氧化氮合酶mRNA起始区域互补的反义寡核苷酸，可使高钠摄入的大鼠血压升高14±1 mmHg。向高盐对照大鼠的不同组间质中输注生理盐水或乱序寡核苷酸探针未能改变血压。向肾髓质间质输注反义寡核苷酸可使肾髓质中神经型一氧化氮合酶水平显著降低53±8%，并使肾髓质总一氧化氮合酶活性降低28±8%。在输注反义寡核苷酸的大鼠中，未检测到诱导型一氧化氮合酶或β-肌动蛋白水平的改变。为了证实反义寡核苷酸的数据，我们给另一组高盐饮食的大鼠施用了一种作用机制不同的神经型一氧化氮合酶抑制剂7-硝基吲唑。直接向肾髓质间质输注这种选择性酶抑制剂可使高钠饮食的大鼠平均动脉压显著升高（15±6 mmHg），并使肾髓质总一氧化氮合酶活性降低37±12%。本实验证明了在高盐饮食情况下，一氧化氮合酶神经亚型在血压长期控制中的作用。
