Cardiac angiotensin II receptors are upregulated by long-term inhibition of nitric oxide synthesis in rats

Makoto Katoh, Kensuke Egashira, Makoto Usui, Toshihiro Ichiki, Hideharu Tomita, Hiroaki Shimokawa, Hiromi Rakugi, Akira Takeshita

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    118 Citations (Scopus)


    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 N(ω)-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.

    Original languageEnglish
    Pages (from-to)743-751
    Number of pages9
    JournalCirculation research
    Issue number7
    Publication statusPublished - Oct 5 1998

    All Science Journal Classification (ASJC) codes

    • Physiology
    • Cardiology and Cardiovascular Medicine


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