Relaxin improves renal function and histology in aging Munich Wistar rats.
Administration of recombinant human relaxin (rhRLX) to conscious, chronically instrumented rats increases GFR and effective renal plasma flow (ERPF) and decreases effective renal vascular resistance (ERVR) with no significant change in mean arterial pressure. The Munich Wistar albino rat shows progressive chronic nephrosis with age and therefore was used to determine the functional and histologic consequences of rhRLX on matrix remodeling in the kidney of older rats. RLX-infused rats showed increased GFR and ERPF with decreased ERVR. Furthermore, in a double-blinded examination, the renal histology showed a significant decrease in glomerular and tubular collagen deposition in the rhRLX-infused aged rats. During short-term rhRLX administration (24 h), gelatinase activity was found to be essential for renal vasodilation and hyperfiltration. Surprisingly, after 20 d, improved renal function was insensitive to the inhibition of gelatinase activity, suggesting that collagen degradation in these rats had permanently altered the matrix of the renal vasculature. In conclusion, long-term administration of rhRLX improves renal function and ameliorates renal pathology in an aging rat model. The biphasic action of rhRLX on the kidney indicates that, acutely, the vessels dilate, causing increased filtration and renal blood flow with decreased vascular resistance as a result of upregulation of gelatinase activity. Subsequently, the renal vessels undergo alteration in supporting matrix, showing increased blood supply even in the face of acute matrix metalloproteinase inhibition, most likely as a result of the inhibitory properties of RLX on collagen production or increased collagen breakdown.
Danielson
Lee A
LA
University of New Mexico, MSC09 5250, Albuquerque, NM 87131-0001, USA. ldanielson@salud.unm.edu
Welford
Angela
A
Harris
Alexis
A
D000375:Aging / Q000187:drug effects* / Q000473:pathology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007668:Kidney / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D009401:Nephrosis / Q000473:pathology* / Q000503:physiopathology* / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D012065:Relaxin / Q000008:administration & dosage*; D012079:Renal Circulation / Q000187:drug effects*
D012065:Relaxin