Age-dependent renal cortical microvascular loss in female mice

Abstract

LO. Age-dependent renal cortical microvascular loss in female mice. Am J Physiol Endocrinol Metab 302: E979 -E986, 2012. First published February 7, 2012 doi:10.1152/ajpendo.00411.2011.-Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18 -22 mo. Another comparable group was replenished with estrogen after Ovx (OvxϩE), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20 -200 m) was decreased in all aged groups compared with young controls (30.3 Ϯ 5.8 vessels/mm 2 , P Ͻ 0.05), but tended to be lower in sham compared with Ovx and OvxϩE (9.9 Ϯ 1.7 vs. 17.2 Ϯ 4.2 and 18 Ϯ 3.0 vessels/mm 2 , P ϭ 0.08 and P ϭ 0.02, respectively). Cortical density of larger microvessels (200 -500 m) decreased only in aged sham (P ϭ 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in OvxϩE, in association with downregulated transforming growth factor-␤ signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen.

Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone

“…Similarly, the first reported observation of murine ochronosis was in a tyrosinemic mouse with extensive kidney damage 14. As age-related loss of renal function normally occurs in humans (beginning in the fourth decade)22 and mice,23 declining excretion in the ageing kidney may lead to rising plasma HGA concentration, co-incident with the midlife observation of pathological, ochronotic changes.…”

Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner

“…Our findings are in line with previous literature studying age-dependent progression of renal damage in female mice. Urbieta-Caceres et al suggested that aging-induced renal interstitial fibrosis in female mice was mediated by loss of endogenous estrogen [ 30 ]. Zheng et al reported that female mice developed progressive glomerulosclerosis after menopause [ 31 ].…”

Renal Vascular Structure and Rarefaction

“…Smaller arterioles and capillaries are the first to suffer a vascular dropout when facing acute or chronic insults and the lost of MV circulation via structural rarefaction has been shown to have an impact on renal hemodynamics (5, 81, 127) and function (103, 131). Furthermore, it has been shown that renal MV structural rarefaction plays an important role in the reduction of RBF and GFR with normal aging (149), indicating that vascular regression is also a physiological event.…”