Otsuka F, Ogura T, Kataoka H, Kishida M, Takahashi M, Mimura Y, Yamauchi T, Makino H
Department of Medicine III, Okayama University Medical School, 2-5-1 Shikata-cho, 700-8558, Okayama, Japan.
J Steroid Biochem Mol Biol. 2000 Oct;74(3):125-36. doi: 10.1016/s0960-0760(00)00096-0.
We have investigated the in vivo effect of chronic blockade of Ca(2+)-channels and angiotensin II type 1 (AT(1))-receptors on aldosterone (Aldo)-synthesis in the adrenal glands of spontaneously hypertensive rats (SHR). Male SHR were administered Ca(2+)-antagonist, amlodipine (10 mg/kg per day) or AT(1)-receptor-antagonist, TCV-116 (1 mg/kg per day) from 7 until 11 weeks of age. Systolic blood pressure (SBP) and heart rate (HR) were significantly higher in SHR than Wistar-Kyoto (WKY) rats. Both treatments resulted in equivalent and significant reduction in SBP in SHR. Aldo-secretion in SHR, which was significantly higher than in WKY rats, was profoundly suppressed by TCV-116 compared with amlodipine. Both treatments resulted in thickening of the zona glomerulosa, which immunohistochemically contains Aldo, at the end of therapy. Competitive reverse transcription-polymerase chain reaction (RT-PCR) showed that CYP11A (P450scc) mRNA regulating the first step of Aldo-synthesis was significantly reduced from week 9 of age by amlodipine, and that CYP11B2 (P450aldo) mRNA regulating the last step of Aldo-synthesis was potently suppressed from 9 weeks of age by TCV-116. Our results indicate that chronic treatment with different antihypertensive agents directly modulates adrenocortical aldosterone synthesis in SHR in vivo via different mechanisms.
我们研究了慢性阻断钙通道和血管紧张素II 1型（AT(1)）受体对自发性高血压大鼠（SHR）肾上腺醛固酮（Aldo）合成的体内影响。雄性SHR从7周龄至11周龄期间给予钙拮抗剂氨氯地平（每天10 mg/kg）或AT(1)受体拮抗剂TCV-116（每天1 mg/kg）。SHR的收缩压（SBP）和心率（HR）显著高于Wistar-Kyoto（WKY）大鼠。两种治疗均使SHR的SBP显著降低且效果相当。与氨氯地平相比，TCV-116可显著抑制SHR中醛固酮的分泌，而SHR中醛固酮的分泌显著高于WKY大鼠。两种治疗在治疗结束时均导致醛固酮所在的球状带增厚。竞争性逆转录-聚合酶链反应（RT-PCR）显示，调节醛固酮合成第一步的CYP11A（P450scc）mRNA从9周龄起被氨氯地平显著降低，而调节醛固酮合成最后一步的CYP11B2（P450aldo）mRNA从9周龄起被TCV-116有效抑制。我们的结果表明，用不同的抗高血压药物进行慢性治疗可通过不同机制在体内直接调节SHR肾上腺皮质醛固酮的合成。
