Relaxin Attenuates Organ Fibrosis via an Angiotensin Type 2 Receptor Mechanism in Aged Hypertensive Female Rats
| Autor: | Robert E Widdop, Katrina M Mirabito Colafella, Tracey Gaspari, Edmund Kwok, Anita A. Pinar, Giannie Barsha, Sarah L. Walton, Kate M. Denton, Chrishan S. Samuel, Lucinda M. Hilliard Krause |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Cardiac fibrosis Renal function Receptor Angiotensin Type 2 Fibrosis Rats Inbred SHR Internal medicine medicine.artery medicine Animals Original Investigation Relaxin Aorta Kidney Proteinuria business.industry General Medicine medicine.disease Recombinant Proteins Rats Endocrinology medicine.anatomical_structure Blood pressure Hypertension Female medicine.symptom business |
| Zdroj: | Kidney360 |
| ISSN: | 2641-7650 |
| DOI: | 10.34067/kid.0002722021 |
| Popis: | BACKGROUND: The antifibrotic effects of recombinant human relaxin (RLX) in the kidney are dependent on an interaction between its cognate receptor (RXFP1) and the angiotensin type 2 receptor (AT(2)R) in male models of disease. Whether RLX has therapeutic effects, which are also mediated via AT(2)R, in hypertensive adult and aged/reproductively senescent females is unknown. Thus, we determined whether treatment with RLX provides cardiorenal protection via an AT(2)R-dependent mechanism in adult and aged female stroke-prone spontaneously hypertensive rats (SHRSPs). METHODS: In 6-month-old (6MO) and 15-month-old ([15MO]; reproductively senescent) female SHRSP, systolic BP (SBP), GFR, and proteinuria were measured before and after 4 weeks of treatment with vehicle (Veh), RLX (0.5 mg/kg per day s.c.), or RLX+PD123319 (AT(2)R antagonist; 3 mg/kg per day s.c.). Aortic endothelium–dependent relaxation and fibrosis of the kidney, heart, and aorta were assessed. RESULTS: In 6MO SHRSP, RLX significantly enhanced GFR by approximately 25% (P=0.001) and reduced cardiac fibrosis (P=0.01) as compared with vehicle-treated counterparts. These effects were abolished or blunted by PD123319 coadministration. In 15MO females, RLX reduced interstitial renal (P=0.02) and aortic (P=0.003) fibrosis and lowered SBP (13±3 mm Hg; P=0.04) relative to controls. These effects were also blocked by PD123319 cotreatment (all P=0.05 versus RLX treatment alone). RLX also markedly improved vascular function by approximately 40% (P |
| Databáze: | OpenAIRE |
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