Hypercholesterolemia impairs nonstenotic kidney outcomes after reversal of experimental renovascular hypertension

Dong Sun, Zhi Chen, Alfonso Eirin, Xiang Yang Zhu, Amir Lerman, Stephen C Textor, Lilach O Lerman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

BACKGROUND 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. METHODS 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. RESULTS 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 PGF2? isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS 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.

Original languageEnglish (US)
Pages (from-to)853-859
Number of pages7
JournalAmerican Journal of Hypertension
Volume29
Issue number7
DOIs
StatePublished - 2016

Fingerprint

Renovascular Hypertension
Hypercholesterolemia
Kidney
Hypertension
Wounds and Injuries
Oxidative Stress
Isoprostanes
Sus scrofa
Dinoprost
Renal Circulation
Vasoconstrictor Agents
Endothelin-1
Renal Artery
Glomerular Filtration Rate
Atherosclerosis
Arterial Pressure
Fibrosis
Swine

Keywords

  • Blood pressure
  • Endothelin-1
  • Hypercholesterolemia
  • Hypertension
  • Oxidative stress
  • Renovascular hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

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title = "Hypercholesterolemia impairs nonstenotic kidney outcomes after reversal of experimental renovascular hypertension",
abstract = "BACKGROUND 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. METHODS 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. RESULTS 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 PGF2? isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS 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.",
keywords = "Blood pressure, Endothelin-1, Hypercholesterolemia, Hypertension, Oxidative stress, Renovascular hypertension",
author = "Dong Sun and Zhi Chen and Alfonso Eirin and Zhu, {Xiang Yang} and Amir Lerman and Textor, {Stephen C} and Lerman, {Lilach O}",
year = "2016",
doi = "10.1093/ajh/hpv222",
language = "English (US)",
volume = "29",
pages = "853--859",
journal = "American Journal of Hypertension",
issn = "0895-7061",
publisher = "Oxford University Press",
number = "7",

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T1 - Hypercholesterolemia impairs nonstenotic kidney outcomes after reversal of experimental renovascular hypertension

AU - Sun, Dong

AU - Chen, Zhi

AU - Eirin, Alfonso

AU - Zhu, Xiang Yang

AU - Lerman, Amir

AU - Textor, Stephen C

AU - Lerman, Lilach O

PY - 2016

Y1 - 2016

N2 - BACKGROUND 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. METHODS 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. RESULTS 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 PGF2? isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS 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.

AB - BACKGROUND 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. METHODS 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. RESULTS 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 PGF2? isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS 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.

KW - Blood pressure

KW - Endothelin-1

KW - Hypercholesterolemia

KW - Hypertension

KW - Oxidative stress

KW - Renovascular hypertension

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