Choi K C, Woo Y J, Park J W, Lee J, Kim W J, Yoo K J, Yoo K S, Kang Y J
Department of Internal Medicine, Chonnam University Medical School, Kwangju, Korea.
Korean J Intern Med. 1994 Jul;9(2):99-104. doi: 10.3904/kjim.1994.9.2.99.
Hypertension is commonly associated with an endothelial dysfunction that may contribute to the rise in blood pressure. Little information has been available so far on the role of endothelium-derived nitric oxide(EDNO) in renin-dependent, 2-kidney, 1 clip(2KIC) hypertension. The present study was aimed to determine a role for EDNO in the development and maintenance of 2KIC hypertension.
The effects of blocking synthesis or supplementation with precursor of EDNO on the development of hypertension were determined in 2KIC rats. Vascular responses to acetylcholine, nitroprusside, atrial natriuretic peptide and nifedipine were examined in 7- and 12-week hypertensive 2KIC rats.
NG-nitro-L-arginine-methyl ester caused a sustained increase of blood pressure in normal rats, while it was only partially associated with a more pronounced increase of blood pressure in the developmental phase of hypertension in 2KIC rats. In 7-week and 12-week hypertensive rats, phenylephrine-induced contraction of the isolated thoracic aortic rings was more sensitive compared with control. Their acetylcholine-induced relaxation was attenuated while the responses to nitroprusside or atrial natriuretic peptide were unaltered. Although their blood pressure did not differ between 7-week and 12-week hypertensive groups, the attenuation in the acetylcholine-induced relaxation was more prominent in the latter with a longer duration of hypertension. Indomethacin did not affect the attenuated relaxation to acetylcholine. The relaxation response to nifedipine was more pronounced in 2KIC rats.
These results indicate that ENDO has little influence of the 2KIC hypertension, at least during its developmental phase, which is associated with an activated reninangiotensin system. The chronic stage of 2KIC hypertension, however, is associated with an endothelial dysfunction which may contribute to the enhanced vasoconstriction and sustained high blood pressure.
高血压通常与内皮功能障碍相关，内皮功能障碍可能导致血压升高。迄今为止，关于内皮源性一氧化氮（EDNO）在肾素依赖性二肾一夹（2KIC）高血压中的作用，几乎没有相关信息。本研究旨在确定EDNO在2KIC高血压发生和维持中的作用。
在2KIC大鼠中，测定阻断EDNO合成或补充其前体对高血压发生的影响。检测7周龄和12周龄高血压2KIC大鼠对乙酰胆碱、硝普钠、心房利钠肽和硝苯地平的血管反应。
NG-硝基-L-精氨酸甲酯使正常大鼠血压持续升高，而在2KIC大鼠高血压发展阶段，它仅部分与血压更明显的升高相关。在7周龄和12周龄高血压大鼠中，苯肾上腺素诱导的离体胸主动脉环收缩比对照组更敏感。它们对乙酰胆碱诱导的舒张减弱，而对硝普钠或心房利钠肽的反应未改变。尽管7周龄和12周龄高血压组之间血压无差异，但乙酰胆碱诱导的舒张减弱在后者更明显，且高血压持续时间更长。吲哚美辛不影响对乙酰胆碱减弱的舒张反应。2KIC大鼠对硝苯地平的舒张反应更明显。
这些结果表明，至少在其发展阶段，内皮源性一氧化氮对2KIC高血压影响很小，这与肾素-血管紧张素系统激活有关。然而，2KIC高血压的慢性阶段与内皮功能障碍相关，这可能导致血管收缩增强和血压持续升高。
