Relaxin does not improve Angiotensin II-induced target-organ damage.
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.
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Nadine
N
Haase
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Julianna
J
Rugor
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Lukasz
L
Przybyl
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Fatimunnisa
F
Qadri
Experimental and Clinical Research Center, a joint cooperation between the Max-Delbrueck Center for Molecular Medicine and the Charité Medical Faculty, Berlin, Germany.
Dominik N
DN
Müller
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.
Ralf
R
Dechend
D000419:Albuminuria / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D000804:Angiotensin II / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D006332:Cardiomegaly / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D011994:Recombinant Proteins / Q000494:pharmacology; D012065:Relaxin / Q000494:pharmacology*; D012083:Renin / Q000235:genetics / Q000378:metabolism
D011994:Recombinant Proteins; D000804:Angiotensin II; D012065:Relaxin; D012083:Renin