Simko F, Matúsková J, Lupták I, Pincíková T, Krajcírovicová K, Stvrtina S, Pomsár J, Pelouch V, Paulis L, Pechánová O
Department of Pathophysiology, Comenius University, Bratislava, Slovak Republic.
Physiol Res. 2007;56 Suppl 2:S25-S32. doi: 10.33549/physiolres.931394. Epub 2007 Sep 5.
Aldosterone receptor antagonist, spironolactone, has been shown to prevent remodeling of the heart in several models of left ventricular hypertrophy. The aim of the present study was to determine whether the treatment with spironolactone can prevent hypertension, reduction of tissue nitric oxide synthase activity and left ventricular (LV) and aortic remodeling in N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. Four groups of rats were investigated: control, spironolactone (200 mg/kg), L-NAME (40 mg/kg) and L-NAME + spironolactone (in corresponding dosage). Animals were studied after 5 weeks of treatment. The decrease of NO-synthase activity in the LV and kidney was associated with the development of hypertension and LV hypertrophy, with increased DNA concentration in the LV, and remodeling of the aorta in the L-NAME group. Spironolactone prevented the inhibition of NO-synthase activity in the LV and kidney and partially attenuated hypertension and LVH development and the increase in DNA concentration. However, remodeling of the aorta was not prevented by spironolactone treatment. We conclude that the aldosterone receptor antagonist spironolactone improved nitric oxide production and partially prevented hypertension and LVH development without preventing hypertrophy of the aorta in NO-deficient hypertension. The reactive growth of the heart and aorta seems to be controlled by different mechanisms in L-NAME-induced hypertension.
醛固酮受体拮抗剂螺内酯已被证明在几种左心室肥厚模型中可预防心脏重塑。本研究的目的是确定螺内酯治疗是否能预防N（G）-硝基-L-精氨酸甲酯（L-NAME）诱导的高血压、组织一氧化氮合酶活性降低以及左心室（LV）和主动脉重塑。研究了四组大鼠：对照组、螺内酯（200 mg/kg）、L-NAME（40 mg/kg）和L-NAME +螺内酯（相应剂量）。治疗5周后对动物进行研究。L-NAME组左心室和肾脏中NO合酶活性的降低与高血压和左心室肥厚的发展相关，左心室DNA浓度增加，主动脉重塑。螺内酯可预防左心室和肾脏中NO合酶活性的抑制，并部分减轻高血压和左心室肥厚的发展以及DNA浓度的增加。然而，螺内酯治疗并不能预防主动脉重塑。我们得出结论，醛固酮受体拮抗剂螺内酯可改善一氧化氮生成，并部分预防高血压和左心室肥厚的发展，但不能预防NO缺乏性高血压中主动脉的肥厚。在L-NAME诱导的高血压中，心脏和主动脉的反应性生长似乎受不同机制控制。
