Relaxin therapy reverses large artery remodeling and improves arterial compliance in senescent spontaneously hypertensive rats.
Hypertension and aging are associated with large artery structural remodeling and stiffening, which are known to increase cardiovascular risk. Relaxin is a peptide hormone with potent antifibrotic action in multiple organs. Although relaxin is able to reduce peripheral vascular resistance and improve arterial compliance in rats, it remains unclear whether the improvement in compliance is indirectly attributed to a vasodilatory action or whether relaxin is able to reverse arterial remodeling and stiffening directly in aged hypertensive animals. Senescent spontaneously hypertensive rats (17 months old) were treated with relaxin for 2 weeks (0.5 mg/kg per day) followed by a 1-week washout period. We determined large artery compliance using in vivo and in vitro techniques and quantified arterial remodeling by morphological and chemical means. Relaxin therapy significantly reversed aortic remodeling (ie, increases in vessel size, wall thickness, and collagen content) and improved arterial compliance, effects independent of its vasodilatory action. In relaxin-treated spontaneously hypertensive rats, arterial collagen content showed a greater reduction (-31%; P<0.05) than that of elastin (-8%), resulting in an increased elastin:collagen ratio (0.63+/-0.03 versus 0.47+/-0.02; P<0.05). In conclusion, our results demonstrated that relaxin is potent in mediating reversal of arterial remodeling and improving arterial structural compliance in aged hypertensive rats.
Xu
Qi
Q
Baker IDI Heart and Diabetes Institute, St Kilda Road Central, Melbourne, PO Box 6492, Victoria 8008, Australia.
Chakravorty
Arindam
A
Bathgate
Ross A D
RA
Dart
Anthony M
AM
Du
Xiao-Jun
XJ
D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects*; D002302:Cardiac Output / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism / Q000494:pharmacology; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D011674:Pulse; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012065:Relaxin / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D012065:Relaxin; D003094:Collagen; D004549:Elastin