title: Sex-specific differences in age-dependent progression of aortic dysfunction and related cardiac remodeling in spontaneously hypertensive rats.
abstract: Evidence of sex-specific differences in renin-angiotensin-system (RAS) and arterial pressure has been shown in many mammals, including spontaneously hypertensive rats (SHRs). Although SHRs have been used extensively as a leading experimental model of hypertension, the effects of sex-specific differences in RAS on aortic function and related cardiac remodeling during aging and hypertension have not been documented in detail. We examined structural and functional changes in aorta and heart of female and male SHRs at the ages of 5, 14, 29, and 36 wk. SHRs of both sexes were hypertensive from 14 wk. Aortic endothelial dysfunction and fibrosis, left ventricular (LV) hypertrophy, and cardiac fibrosis were evident at the age of 29 wk in male SHRs but first appeared only at the age of 36 wk in female SHRs. There was a pronounced delay of matrix metalloproteinase-2 activity in the aorta and heart of female SHRs, which was associated with preservation of 40% more elastin and less extensive cardiac fibrosis than in males. At 5, 29, and 36 wk of age, female SHRs showed higher levels of aortic and myocardial AT2R and MasR mRNA and decreased ANG II-mediated aortic constriction. Although female SHRs had increased relaxation to AT2R stimulation at 5 and 29 wk compared with males, this difference disappeared at 36 wk of age. This study documents sex-specific differences in the temporal progression of aortic dysfunction and LV hypertrophy in SHRs, which are independent of arterial pressure and are apparently mediated by higher AT2R expression in the heart and aorta of female SHRs.
authors.affiliation: Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Suzan
authors.initials: S
authors.lastname: Al-Gburi
authors.affiliation: Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany; Andreas.Deussen@tu-dresden.de.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Deussen
authors.affiliation: Clinical Sensoring and Monitoring, Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Roberta
authors.initials: R
authors.lastname: Galli
authors.affiliation: Institute of Pathology, University Hospital, Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; and.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Muders
authors.affiliation: Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zatschler
authors.affiliation: Department of Anatomy, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Neisser
authors.affiliation: Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Müller
authors.affiliation: Department of Physiology, Faculty of Medicine, Technische Universität Dresden, Dresden, Germany.
authors.forename: Irakli
authors.initials: I
authors.lastname: Kopaliani
mesh_terms: D000375:Aging; D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D006973:Hypertension / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012727:Sex Characteristics; D020257:Ventricular Remodeling
keywords: angiotensin type 2 receptor; aortic remodeling; cardiac remodeling; renin-angiotensin-system; sex characteristics