Haase Nadine, Rugor Julianna, Przybyl Lukasz, Qadri Fatimunnisa, Müller Dominik N, Dechend Ralf
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany; Department of Cardiology and Nephrology, HELIOS-Klinikum Berlin, Berlin, Germany.
PLoS One. 2014 Apr 7;9(4):e93743. doi: 10.1371/journal.pone.0093743. eCollection 2014.
Relaxin is a corpus-luteum produced protein hormone with vasodilatatory, anti-fibrotic, and angiogenic properties that are opposite to angiotensin (Ang) II. We investigated whether or not relaxin ameliorates Ang II-induced target-organ damage. We used double transgenic rats harboring both human renin and angiotensinogen genes (dTGR) that develop severe hypertension, target-organ damage, and die untreated within 7-8 weeks. Recombinant relaxin at a low (26 μg/kg/d) and a high dose (240 μg/kg/d) was given to 4 week-old dTGR and age-matched Sprague-Dawley rats (SD). Systolic blood pressure increased progressively in untreated dTGRs from 162 ± 3 mmHg at week 5 to 225 ± 5 mmHg at week 7. Relaxin had no effect on blood pressure whereas SD rats were normotensive (106 ± 1 mmHg). Untreated and relaxin-treated dTGR had similarly severe cardiac hypertrophy indices. Relaxin did not ameliorate albuminuria and did not prevent matrix-protein deposition in the heart and kidney in dTGR. Finally, relaxin treatment did not reduce mortality. These data suggest that pharmacological doses of relaxin do not reverse severe effects of Ang II.
松弛素是一种由黄体产生的蛋白质激素，具有血管舒张、抗纤维化和血管生成特性，这些特性与血管紧张素（Ang）II相反。我们研究了松弛素是否能改善Ang II诱导的靶器官损伤。我们使用了同时携带人肾素和血管紧张素原基因的双转基因大鼠（dTGR），这些大鼠会发展为严重高血压、靶器官损伤，未经治疗在7-8周内死亡。将低剂量（26μg/kg/d）和高剂量（240μg/kg/d）的重组松弛素给予4周龄的dTGR和年龄匹配的Sprague-Dawley大鼠（SD）。未治疗的dTGR收缩压从第5周的162±3 mmHg逐渐升高到第7周的225±5 mmHg。松弛素对血压没有影响，而SD大鼠血压正常（106±1 mmHg）。未治疗和接受松弛素治疗的dTGR具有同样严重的心脏肥大指数。松弛素不能改善蛋白尿，也不能防止dTGR心脏和肾脏中的基质蛋白沉积。最后，松弛素治疗不能降低死亡率。这些数据表明，药理学剂量的松弛素不能逆转Ang II的严重影响。
