Takeda Y, Yoneda T, Demura M, Miyamori I, Mabuchi H
Second Department of Internal Medicine, Department of Health Sciences, School of Medicine, Kanazawa University, Kanazawa, Japan.
Hypertension. 2000 Oct;36(4):495-500. doi: 10.1161/01.hyp.36.4.495.
Aldosterone is synthesized in extra-adrenal tissues, both blood vessels and brain. We undertook the present study to determine whether the rat heart produces aldosterone and to investigate the effects of adrenalectomy, ACE inhibition, and angiotensin II on aldosterone synthesis in the heart. To clarify the pathophysiological role of cardiac aldosterone in the hypertensive heart, we compared the synthesis of aldosterone in the hearts of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats. The effects of the aldosterone antagonist spironolactone on myocardial hypertrophy in adrenalectomized SHRSP were also studied. Isolated rat hearts were perfused for 2 hours, and the perfusate was analyzed with HPLC and mass spectrometry. The activity of aldosterone synthase was estimated on the basis of the conversion of [(14)C]deoxycorticosterone to [(14)C]aldosterone. The levels of aldosterone synthase gene (CYP11B2) mRNA were determined with competitive polymerase chain reaction. Aldosterone production, the activity of aldosterone synthase, and the expression of CYP11B2 mRNA were increased in hearts from adrenalectomized rats and rats treated with angiotensin II. ACE inhibitors decreased cardiac aldosterone synthesis. Cardiac aldosterone, aldosterone synthase activity, and CYP11B2 mRNA levels in hearts from 2- and 4-week-old SHRSP were significantly greater than those of age-matched Wistar-Kyoto rats. Spironolactone prevented cardiac hypertrophy in adrenalectomized SHRSP. These results suggest that the rat heart produces aldosterone and that endogenous cardiac aldosterone may affect cardiac function and hypertrophy in hypertension in rats.
醛固酮在肾上腺外组织（血管和脑）中合成。我们开展本研究以确定大鼠心脏是否产生醛固酮，并研究肾上腺切除术、血管紧张素转换酶（ACE）抑制以及血管紧张素II对心脏中醛固酮合成的影响。为阐明心脏醛固酮在高血压心脏中的病理生理作用，我们比较了易卒中型自发性高血压大鼠（SHRSP）心脏与Wistar-Kyoto大鼠心脏中醛固酮的合成情况。还研究了醛固酮拮抗剂螺内酯对肾上腺切除的SHRSP心肌肥大的影响。将离体大鼠心脏灌注2小时，并用高效液相色谱法（HPLC）和质谱法分析灌注液。基于[（14）C]脱氧皮质酮向[（14）C]醛固酮的转化来估计醛固酮合酶的活性。用竞争性聚合酶链反应测定醛固酮合酶基因（CYP11B2）mRNA的水平。肾上腺切除大鼠和用血管紧张素II处理的大鼠心脏中的醛固酮生成、醛固酮合酶活性以及CYP11B2 mRNA的表达均增加。ACE抑制剂降低心脏醛固酮的合成。2周龄和4周龄SHRSP心脏中的心脏醛固酮、醛固酮合酶活性以及CYP11B2 mRNA水平显著高于年龄匹配的Wistar-Kyoto大鼠。螺内酯可预防肾上腺切除的SHRSP的心肌肥大。这些结果表明大鼠心脏可产生醛固酮，并且内源性心脏醛固酮可能影响大鼠高血压时的心脏功能和肥大。
