Department of Biomedical Sciences, University of Missouri, Columbia, MO 65211, USA.
Vet Pathol. 2011 Nov;48(6):1125-33. doi: 10.1177/0300985810391109. Epub 2010 Dec 15.
The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.
本研究旨在探讨慢性抑制一氧化氮合酶（NOS）对猪的致密斑（MD）中环氧化酶-2（COX-2）表达的影响，以及对相关蛋白表达的影响。成年雌性尤卡坦猪给予自来水（对照组，n=6）或含 N（G）-硝基-L-精氨酸甲酯（L-NAME，100mg/L，n=5）的水，至少 30 天。肾脏的重复样本被固定或速冻。L-NAME 组 MD 中的 COX-2 mRNA 表达显著上调（P=0.0082），COX-2 蛋白也明显增加。血浆肾素活性也随 L-NAME 治疗而增加（对照组，0.34±0.08ng/ml；L-NAME，1.26±0.03ng/ml；P=0.00000003）。两组之间诱导型 NOS 或肾素蛋白的表达或血清电解质浓度均无差异。总之，NOS 的慢性抑制导致 MD 中的 COX-2 上调，可能是为了弥补一氧化氮的损失。COX-2 产物的增加可能抵消肾小动脉收缩并维持肾素释放。
