抗高血压治疗对自发性高血压大鼠心脏肌浆网钙转运的影响。

Effect of antihypertensive therapy on calcium transport by cardiac sarcoplasmic reticulum of SHRs.

作者信息

Limas C J, Spier S S

出版信息

Cardiovasc Res. 1980 Dec;14(12):692-9. doi: 10.1093/cvr/14.12.692.

DOI:10.1093/cvr/14.12.692

Abstract

Cardiac hypertrophy develops during the course of blood pressure elevation in spontaneously hypertensive rats (SHRs) and is associated with defective calcium transport by cardiac sarcoplasmic reticulum (SR). AT 20 weeks of age, calcium uptake is reduced in SHRs (42 +/- 1.3 vs 64 +/- 1.6 nmol X mg-1 X min-1 in age-matched normotensive Wistar-Kyoto rats, P less than 0.01), while Ca2+ ATPase activity is enhanced (44 +/- 1.1 vs 35 +/- 0.7 nmol X mg-1 X min-1 in WKYs, P = 0.02); this results in low stoichiometry between calcium uptake and ATP hydrolysis in SHRs. The steady-state levels of the phosphoprotein intermediate [EP] of the transport ATPase are higher in normotensive rats (0.97 +/- 0.1 vs 0.67 +/- 0.08 nmol X mg-1 in SHRs, P less than 0.01) but the Ca2+- and ATP-dependency are similar in the two groups. In order to study the relative roles of hypertension and cardiac hypertrophy in the depression of SHR function, 20-week old SHRs and normotensive rats were treated for 10 weeks with either hydralazine (100 mg X litre-1) or alpha-methyldopa (8 g X litre-1). Both therapeutic regimens resulted in near normalisation of blood pressure of SHRs (hydralazine: 18.1 +/- 0.5 kPa [136 +/- 4 mmHg]; alpha-methyldopa 17.6 +/- kPa [132 +/- 3 mmHg]). Regression of cardiac hypertrophy, however, was seen only in the alpha-methyldopa-treated group, as judged by changes in left ventricular weight, RNA/DNA ratio, and hydroxyproline content. Furthermore, improvement in calcium transport capacity by the SHR, as reflected in higher calcium uptake and stoichiometric ratio between uptake and ATP hydrolysis, was found after alpha-methyldopa, but not hydralazine treatment. These results indicate that reversal of cardiac hypertrophy is required for improvement in calcium transport by cardiac SR after antihypertensive therapy of SHRs.

摘要

自发性高血压大鼠（SHR）在血压升高过程中会出现心脏肥大，且与心肌肌浆网（SR）钙转运缺陷有关。在20周龄时，SHR的钙摄取减少（42±1.3对年龄匹配的正常血压Wistar-Kyoto大鼠的64±1.6 nmol·mg⁻¹·min⁻¹，P<0.01），而Ca²⁺ATP酶活性增强（WKY大鼠为35±0.7 nmol·mg⁻¹·min⁻¹，SHR为44±1.1 nmol·mg⁻¹·min⁻¹，P = 0.02）；这导致SHR中钙摄取与ATP水解之间的化学计量比降低。正常血压大鼠中转运ATP酶的磷蛋白中间体[EP]的稳态水平较高（SHR中为0.67±0.08 nmol·mg⁻¹，正常血压大鼠中为0.97±0.1 nmol·mg⁻¹，P<0.01），但两组中Ca²⁺和ATP依赖性相似。为了研究高血压和心脏肥大在SHR功能抑制中的相对作用，用肼屈嗪（100 mg·L⁻¹）或α-甲基多巴（8 g·L⁻¹）对20周龄的SHR和正常血压大鼠进行10周治疗。两种治疗方案均使SHR的血压接近正常化（肼屈嗪：18.1±0.5 kPa [136±4 mmHg]；α-甲基多巴17.6±kPa [132±3 mmHg]）。然而，根据左心室重量、RNA/DNA比率和羟脯氨酸含量的变化判断，仅在α-甲基多巴治疗组中观察到心脏肥大的消退。此外，在α-甲基多巴治疗后发现SHR的钙转运能力有所改善，表现为较高的钙摄取以及摄取与ATP水解之间的化学计量比，但肼屈嗪治疗后未出现这种情况。这些结果表明，SHR降压治疗后，心脏肥大的逆转是改善心肌SR钙转运所必需的。