Takeda Y, Miyamori I, Inaba S, Furukawa K, Hatakeyama H, Yoneda T, Mabuchi H, Takeda R
Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Hypertension. 1997 Jan;29(1 Pt 1):45-8. doi: 10.1161/01.hyp.29.1.45.
We have reported that aldosterone is synthesized and cytochrome P450aldo mRNA exists in the vasculature. To clarify the pathophysiological role of vascular aldosterone in hypertension, we compared aldosterone production in the mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats (WKY). The expressions of mRNA of cytochrome P450aldo, mineralocorticoid receptor, and alpha 1, Na,K-ATPase in the mesenteric arteries were compared between the two groups. Aldosterone concentration in the perfusate of the vasculature was measured by radioimmunoassay after purification with high-performance liquid chromatography. Cytochrome P450aldo and mineralocorticoid receptor mRNA levels were quantified by Southern blot analysis of the products of reverse-transcribed polymerase chain reaction. Levels of alpha 1 Na,K-ATPase mRNA were measured by Northern blot analysis. Vascular aldosterone and cytochrome P450aldo mRNA levels of 2-week-old SHRSP were significantly increased compared with those of age-matched WKY. However, vascular aldosterone in 4- and 9-week-old SHRSP did not differ from that in age-matched WKY. Expression levels of mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP were significantly increased compared with those in age-matched WKY. Concentrations of vascular alpha 1 Na,K-ATPase mRNA of 2-, 4-, and 9-week-old SHRSP also were significantly higher than those in age-matched WKY. These results suggest that vascular aldosterone contributes to the pathophysiology of hypertension in SHRSP in the early stage.
我们曾报道血管中可合成醛固酮且存在细胞色素P450aldo mRNA。为阐明血管醛固酮在高血压发病机制中的作用，我们比较了易卒中型自发性高血压大鼠（SHRSP）与Wistar-Kyoto大鼠（WKY）肠系膜动脉中醛固酮的生成情况。比较了两组肠系膜动脉中细胞色素P450aldo、盐皮质激素受体和α1、Na，K-ATP酶的mRNA表达。用高效液相色谱纯化后，通过放射免疫分析法测定血管灌流液中的醛固酮浓度。通过逆转录聚合酶链反应产物的Southern印迹分析对细胞色素P450aldo和盐皮质激素受体mRNA水平进行定量。通过Northern印迹分析测量α1 Na，K-ATP酶mRNA水平。与年龄匹配的WKY相比，2周龄SHRSP的血管醛固酮和细胞色素P450aldo mRNA水平显著升高。然而，4周龄和9周龄SHRSP的血管醛固酮与年龄匹配的WKY并无差异。与年龄匹配的WKY相比，4周龄和9周龄SHRSP血管中盐皮质激素受体mRNA的表达水平显著升高。2周龄、4周龄和9周龄SHRSP的血管α1 Na，K-ATP酶mRNA浓度也显著高于年龄匹配的WKY。这些结果表明，血管醛固酮在早期对SHRSP高血压的病理生理过程有影响。
