title: Hypercholesterolemia Impairs Nonstenotic Kidney Outcomes After Reversal of Experimental Renovascular Hypertension.
abstract: Revascularization of a stenotic renal artery improves kidney function only in select patients with renovascular hypertension (HT) secondary to atherosclerosis. However, the effects of reversal of renovascular HT (RRHT) on the nonstenotic kidney are unclear. We hypothesized that concurrent hypercholesterolemia (HC) attenuates nonstenotic kidney recovery.
  
  
  
  Female domestic pigs were randomized as Normal, renovascular HT, HT+RRHT, HTC (renovascular HT and HC), and HTC+RHT (n = 7 each). RRHT or sham was performed after 6 weeks of HT. Nonstenotic renal blood flow, glomerular filtration rate, and injurious pathways were studied 4 weeks later.
  
  
  
  Mean arterial pressure increased similarly in HT and HTC and decreased after RRHT. Oxidative stress increased in HT and HTC kidneys, and decreased in HT+RRHT, but remained elevated in HTC+RRHT. Renal interstitial fibrosis, glomerulosclerosis, and tubular injury were all attenuated in HT+RRHT, but not HTC+RRHT. Endothelin-1 signaling and PGF2α isoprostane levels were elevated in both HTC and HTC+RRHT pigs.
  
  
  
  RRHT reverses nonstenotic kidney injury in experimental renovascular HT, but concurrent HC blunts regression of kidney injury, possibly due to predominant vasoconstrictors and oxidative stress. These findings reinforce the contribution of the nonstenotic kidney and of prevailing cardiovascular risk factors to irreversibility of kidney dysfunction after revascularization.
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; The Department of Nephrology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China;
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Xiang-Yang
authors.initials: XY
authors.lastname: Zhu
authors.affiliation: The Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Lerman
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA;
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Textor
authors.affiliation: The Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA; The Division of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota, USA. lerman.lilach@mayo.edu.
authors.forename: Lilach O
authors.initials: LO
authors.lastname: Lerman
mesh_terms: D000818:Animals; D005260:Female; D006937:Hypercholesterolemia / Q000150:complications / Q000473:pathology*; D006978:Hypertension, Renovascular / Q000150:complications / Q000473:pathology* / Q000601:surgery; D007668:Kidney / Q000473:pathology*; D011897:Random Allocation; D012078:Renal Artery Obstruction / Q000150:complications / Q000473:pathology* / Q000601:surgery; D012079:Renal Circulation; D013552:Swine
keywords: blood pressure; endothelin-1; hypercholesterolemia; hypertension; oxidative stress; renovascular hypertension.