Bolterman Rodney J, Manriquez Melissa C, Ortiz Ruiz M Clara, Juncos Luis A, Romero J Carlos
Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hypertension. 2005 Oct;46(4):943-7. doi: 10.1161/01.HYP.0000174602.59935.d5. Epub 2005 Aug 8.
There is substantial evidence suggesting that angiotensin II plays an important role in elevating blood pressure of spontaneously hypertensive rats, despite normal plasma renin activity, and that converting enzyme inhibitors (captopril) can effectively normalize blood pressure in the spontaneously hypertensive rats. One mechanism by which angiotensin II induces hypertension is via oxidative stress and endothelin, as seen in subpressor angiotensin II-induced hypertension. In fact, it has been shown that antioxidants lower mean arterial pressure in spontaneously hypertensive rats. However, the relationship between angiotensin II, oxidative stress, and endothelin in the spontaneously hypertensive rats is still relatively undefined. This study examines the relationship between mean arterial pressure, plasma renin activity, angiotensin II, oxidative stress, and endothelin in spontaneously hypertensive rats compared with normotensive Wistar Kyoto rats, and the effects of captopril on this association. Untreated spontaneously hypertensive rats had increased plasma angiotensin II levels despite normal plasma renin activity, oxidative stress, and endothelin. Captopril treatment in spontaneously hypertensive rats lowered mean arterial pressure, angiotensin II, oxidative stress, and endothelin, and increased plasma renin activity. In contrast, captopril increased plasma renin activity (suggesting effective captopril treatment) but did not significantly alter mean arterial pressure, angiotensin II, oxidative stress, or endothelin of Wistar Kyoto rats. These results suggest that in spontaneously hypertensive rats, angiotensin II is a primary instigator of hypertension, and that captopril selectively lowers angiotensin II, oxidant stress, and endothelin, which in turn may contribute to the blood pressure-lowering efficacy of captopril in spontaneously hypertensive rats.
有大量证据表明，尽管自发性高血压大鼠的血浆肾素活性正常，但血管紧张素II在升高其血压方面发挥着重要作用，并且血管紧张素转换酶抑制剂（卡托普利）能够有效使自发性高血压大鼠的血压恢复正常。血管紧张素II诱发高血压的一种机制是通过氧化应激和内皮素，如在亚升压剂量的血管紧张素II诱发的高血压中所见。事实上，已经表明抗氧化剂可降低自发性高血压大鼠的平均动脉压。然而，自发性高血压大鼠中血管紧张素II、氧化应激和内皮素之间的关系仍相对不明确。本研究比较了自发性高血压大鼠与血压正常的Wistar Kyoto大鼠的平均动脉压、血浆肾素活性、血管紧张素II、氧化应激和内皮素之间的关系，以及卡托普利对这种关联的影响。未经治疗的自发性高血压大鼠尽管血浆肾素活性、氧化应激和内皮素正常，但血浆血管紧张素II水平升高。对自发性高血压大鼠进行卡托普利治疗可降低平均动脉压、血管紧张素II、氧化应激和内皮素，并增加血浆肾素活性。相比之下，卡托普利增加了Wistar Kyoto大鼠的血浆肾素活性（表明卡托普利治疗有效），但未显著改变其平均动脉压、血管紧张素II、氧化应激或内皮素。这些结果表明，在自发性高血压大鼠中，血管紧张素II是高血压的主要诱因，并且卡托普利选择性地降低血管紧张素II、氧化应激和内皮素，这反过来可能有助于卡托普利在自发性高血压大鼠中的降压效果。
