Katoh M, Egashira K, Usui M, Ichiki T, Tomita H, Shimokawa H, Rakugi H, Takeshita A
Research Institute of Angiocardiology and Cardiovascular Clinic, Kyushu University School of Medicine, Fukuoka, Japan.
Circ Res. 1998 Oct 5;83(7):743-51. doi: 10.1161/01.res.83.7.743.
It has been shown that nitric oxide (NO) may regulate angiotensin II (Ang II) receptors in vitro. To determine whether the chronic inhibition of NO synthesis upregulates cardiac Ang II receptors in a rat model, we evaluated the in vivo effect of Nomega-nitro-L-arginine methyl ester (L-NAME) on several Ang II receptors and on the expression of AT1 receptor mRNA in heart tissue. The chronic administration of L-NAME to normal rats increased the arterial blood pressure. The number of AT1 and AT2 receptors was increased, with no change in affinity, during the first week of L-NAME administration but returned to control levels after 4 weeks of treatment. The AT1 receptor mRNA was changed parallel to AT1 receptor number. Inflammatory changes (monocyte infiltration and myofibroblast formation) in perivascular areas surrounding coronary vessels and myocardial interstitial spaces were observed during the first week. The immunohistochemistry revealed that myofibroblasts expressed AT1 receptor. AT1 receptor blockade or cotreatment with L-arginine, but not cotreatment with hydralazine, prevented the L-NAME-induced increase in Ang II receptors and inflammatory changes. In conclusion, rat cardiac Ang II receptors are upregulated at an early phase of chronic inhibition of NO synthesis. This may contribute to cardiovascular inflammatory changes in an early phase and to remodeling at the later phase, which occurs after inhibition of NO synthesis.
研究表明，一氧化氮（NO）在体外可能调节血管紧张素II（Ang II）受体。为了确定在大鼠模型中慢性抑制NO合成是否会上调心脏Ang II受体，我们评估了Nω-硝基-L-精氨酸甲酯（L-NAME）对几种Ang II受体以及心脏组织中AT1受体mRNA表达的体内作用。向正常大鼠长期给予L-NAME会升高动脉血压。在给予L-NAME的第一周，AT1和AT2受体的数量增加，亲和力无变化，但在治疗4周后恢复到对照水平。AT1受体mRNA的变化与AT1受体数量平行。在第一周观察到冠状动脉血管周围和心肌间质空间的血管周围区域有炎症变化（单核细胞浸润和成肌纤维细胞形成）。免疫组织化学显示成肌纤维细胞表达AT1受体。AT1受体阻断或与L-精氨酸联合治疗，但不与肼屈嗪联合治疗，可防止L-NAME诱导的Ang II受体增加和炎症变化。总之，在慢性抑制NO合成的早期阶段，大鼠心脏Ang II受体上调。这可能在早期阶段导致心血管炎症变化，并在后期阶段导致重塑，后者发生在抑制NO合成之后。
