Stout Jacob M, Gousset Monette U, Drummond Heather A, Gray Will, Pruett Brandon E, Stec David E
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, 2500 North State St, Jackson, Mississippi.
J Am Soc Hypertens. 2013 Sep-Oct;7(5):328-35. doi: 10.1016/j.jash.2013.04.004. Epub 2013 May 27.
Heme oxygenase-2 (HO-2) is the main isoform responsible for the breakdown of heme and release of carbon monoxide in the vasculature. Vascular-derived carbon monoxide protects against excessive vasoconstriction due to agents such as angiotensin II (Ang II) and in states of deficiency of nitric oxide. The current study was designed to determine the role of HO-2 in the development of renovascular hypertension using HO-2 knockout mice.
Polyurethane cuffs were placed around the left renal artery of male and female HO-2 wild-type (WT), heterozygous (HET), and knockout (KO) mice between 16 and 24 weeks of age to induce renovascular hypertension. After 3 weeks, blood pressure was measured for 5 days, after which time both clipped and unclipped kidneys were harvested.
No differences were observed in the blood pressure of sham mice between the different genotypes of both sexes. Cuffing of the left renal artery resulted in a significant increase in blood pressure in all genotypes of both sexes. In male mice, the increase in blood pressure was significantly greater in HET and KO mice as compared to WT mice (P < .05). This effect was not observed in female mice. Renovascular hypertension resulted in a significant increase (P < .05) in cardiac hypertrophy in male mice, which was not different between the genotypes. In female mice, HET and KO mice exhibited significantly greater (P < .05) cardiac hypertrophy as compared with WT mice.
These results demonstrate a sex-specific effect of HO-2 deficiency on the development of renovascular hypertension and its effects on the heart in response to the increase in blood pressure.
血红素加氧酶-2（HO-2）是负责血红素分解和血管系统中一氧化碳释放的主要同工型。血管源性一氧化碳可防止因血管紧张素II（Ang II）等物质以及一氧化氮缺乏状态导致的过度血管收缩。本研究旨在利用HO-2基因敲除小鼠确定HO-2在肾血管性高血压发展中的作用。
在16至24周龄的雄性和雌性HO-2野生型（WT）、杂合子（HET）和基因敲除（KO）小鼠的左肾动脉周围放置聚氨酯袖带，以诱导肾血管性高血压。3周后，测量5天血压，之后收集夹闭和未夹闭的肾脏。
在不同基因型的两性假手术小鼠中，未观察到血压差异。左肾动脉夹闭导致所有基因型的两性血压显著升高。在雄性小鼠中，与WT小鼠相比，HET和KO小鼠的血压升高显著更大（P < 0.05）。在雌性小鼠中未观察到这种效应。肾血管性高血压导致雄性小鼠心脏肥大显著增加（P < 0.05），各基因型之间无差异。在雌性小鼠中，与WT小鼠相比，HET和KO小鼠表现出显著更大（P < 0.05）的心脏肥大。
这些结果表明，HO-2缺乏对肾血管性高血压的发展及其对血压升高时心脏的影响具有性别特异性效应。
