Abstract
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.
Highlights
Relaxin is a small peptide hormone important in reproduction and pregnancy that is encoded by the RLX gene [1]
Treatment with relaxin did not ameliorate albuminuria compared to vehicle-treated double transgenic human-angiotensinogen and human-renin rat model (dTGR) (57.93766.122 mg/day at week 7)
Vehicle-treated and relaxin treated dTGR showed increased urinary albumin excretion compared to Sprague-Dawley rats (SD) (0.1460.06 mg/day at week 7)
Summary
Relaxin is a small peptide hormone important in reproduction and pregnancy that is encoded by the RLX gene [1]. Relaxin mediates the hemodynamic changes that occur during pregnancy, such as increased cardiac output, increased renal blood flow, and increased arterial compliance. Relaxin increases arterial compliance, cardiac output, and renal blood flow, which are potentially relevant to the treatment of acute heart failure [2,3,4]. A potential role for relaxin in protecting from preeclampsia and the implication that upregulation of the renin-angiotensin system could play a role in that condition caused us to test the hypothesis that relaxin could ameliorate Ang II-induced target-organ damage[8,9,10,11]. Blocking the Renin-Angiotensin System is very successful approach in ameliorating target-organ damage in this model [16], but several anti-inflammatory strategies, such as high dose aspirin, TNF-receptor blocker, steroids, MMF and statins reduced end-organ damage often independent of reducing blood pressure [14,17,18,19]. We investigated whether relaxin is reducing hypertensive target-organ damage in dTGR
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