Ohno Norikazu, Tanaka Takeshi, Kita Taizo, Kubo Kaoru, Shimada Keiji, Yonetani Yukio, Konishi Noboru, Nakashima Toshikatsu
Department of Pharmacology, Nara Medical University, Japan.
J Pharmacol Sci. 2004 Mar;94(3):287-96. doi: 10.1254/jphs.94.287.
The present study was conducted to evaluate the contribution of endothelin (ET) to the pharmacodynamic response to chronic cigarette smoke in spontaneously hypertensive rats (SHR). The contribution of ET was studied consequent to the hemodynamic response following 8 weeks of cigarette smoke by determining the changes in tissue ET-1 content and ET receptors. The blood pressure (BP) at the early phase of smoking and the heart rate (HR) 24 h later were apparently reduced in SHR, while the HR at the early phase was transiently elevated in normotensive Wistar Kyoto (WKY) rats. Tissue ET-1 levels in the hypothalamus, striatum, and cortex of SHR were higher than those in WKY rats, and these higher levels in SHR were reduced by exposure to chronic cigarette smoke. The ET-1 contents in the medulla oblongata and midbrain of both strains were clearly increased by smoke exposure, although the levels of SHR and WKY rats were not different. In addition, the immunoreactivity of the ET type A receptor in the adrenal glands and type B receptor in the kidneys of SHR showed a different response to smoke exposure as compared to WKY rats. Our present findings suggest that the changes of ETs may relate to the pharmacodynamic effects of chronic cigarette smoke.
本研究旨在评估内皮素（ET）在自发性高血压大鼠（SHR）中对慢性香烟烟雾药效学反应的作用。通过测定组织ET-1含量和ET受体的变化，研究了ET在8周香烟烟雾暴露后的血流动力学反应中的作用。吸烟早期SHR的血压（BP）和24小时后的心率（HR）明显降低，而正常血压的Wistar Kyoto（WKY）大鼠在吸烟早期的HR短暂升高。SHR下丘脑、纹状体和皮质中的组织ET-1水平高于WKY大鼠，且SHR中这些较高水平因慢性香烟烟雾暴露而降低。尽管SHR和WKY大鼠的水平无差异，但烟雾暴露均明显增加了两品系大鼠延髓和中脑中的ET-1含量。此外，与WKY大鼠相比，SHR肾上腺中ET A型受体和肾脏中ET B型受体的免疫反应性对烟雾暴露表现出不同的反应。我们目前的研究结果表明，ETs的变化可能与慢性香烟烟雾的药效学作用有关。
