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Experimental coronary artery stenosis accelerates kidney damage in renovascular hypertensive swine.

Sun D, Eirin A, Zhu XY, Zhang X, Crane JA, Woollard JR, Lerman A, Lerman LO - Kidney Int. (2014)

Bottom Line: Systemic levels of PGF2-α isoprostane, a marker of oxidative stress, increased in CAS and CAS plus HT, whereas single-kidney blood flow responses to acetylcholine were significantly blunted only in CAS plus HT compared with sham, HT, and CAS, indicating renovascular endothelial dysfunction.Tissue expression of inflammatory and oxidative markers were elevated in the CAS pig kidney, and further magnified in CAS plus HT, whereas angiogenic factor expression was decreased.Bendavia, a mitochondria-targeted peptide, decreased oxidative stress and improved renal function and structure in CAS.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA [2] Department of Nephrology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.

ABSTRACT
The impact of coronary artery stenosis (CAS) on renal injury is unknown. Here we tested whether the existence of CAS, regardless of concurrent atherosclerosis, would induce kidney injury and magnify its susceptibility to damage from coexisting hypertension (HT). Pigs (seven each) were assigned to sham, left-circumflex CAS, renovascular HT, and CAS plus HT groups. Cardiac and nonstenotic kidney functions, circulating and renal inflammatory and oxidative markers, and renal and microvascular remodeling were assessed 10 weeks later. Myocardial perfusion declined distal to CAS. Systemic levels of PGF2-α isoprostane, a marker of oxidative stress, increased in CAS and CAS plus HT, whereas single-kidney blood flow responses to acetylcholine were significantly blunted only in CAS plus HT compared with sham, HT, and CAS, indicating renovascular endothelial dysfunction. Tissue expression of inflammatory and oxidative markers were elevated in the CAS pig kidney, and further magnified in CAS plus HT, whereas angiogenic factor expression was decreased. Bendavia, a mitochondria-targeted peptide, decreased oxidative stress and improved renal function and structure in CAS. Furthermore, CAS and HT synergistically amplified glomerulosclerosis and renal fibrosis. Thus, mild myocardial ischemia, independent of systemic atherosclerosis, induced renal injury, possibly mediated by increased oxidative stress. Superimposed HT aggravates renal inflammation and endothelial dysfunction caused by CAS, and synergistically promotes kidney fibrosis, providing impetus to preserve cardiac integrity in order to protect the kidney.

No MeSH data available.


Related in: MedlinePlus

Systemic, cardiac, and renal characteristics in Sham, hypertension (HT), coronary artery stenosis (CAS), and CAS+HT pigs. A. Circulating PGF2-α isoprostane. B. Systemic transforming growth-factor (TGF)-β1. C-D. Representative cardiac CT images obtained at the middle left-ventricle (LV). In hypertensive animals (HT and CAS+HT), the LV wall is thickened. The arrow in C shows myocardial lateral wall thinning distal to a high-grade CAS (illustrated in D). E, Cardiac output. F, Myocardial perfusion. G, LV muscle mass (LVMM). H, Glomerular filtration rate (GFR). I, Change in renal blood flow (ΔRBF) in response to acetylcholine (Ach). J, Intratubular concentration (ITC) in the different nephron segments. *P<0.05 vs. Sham; #P<0.05 vs. HT; &P<0.05 vs. CAS.
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Figure 1: Systemic, cardiac, and renal characteristics in Sham, hypertension (HT), coronary artery stenosis (CAS), and CAS+HT pigs. A. Circulating PGF2-α isoprostane. B. Systemic transforming growth-factor (TGF)-β1. C-D. Representative cardiac CT images obtained at the middle left-ventricle (LV). In hypertensive animals (HT and CAS+HT), the LV wall is thickened. The arrow in C shows myocardial lateral wall thinning distal to a high-grade CAS (illustrated in D). E, Cardiac output. F, Myocardial perfusion. G, LV muscle mass (LVMM). H, Glomerular filtration rate (GFR). I, Change in renal blood flow (ΔRBF) in response to acetylcholine (Ach). J, Intratubular concentration (ITC) in the different nephron segments. *P<0.05 vs. Sham; #P<0.05 vs. HT; &P<0.05 vs. CAS.

Mentions: Renal-artery-stenosis increased mean arterial pressure (MAP) in both HT and CAS+HT compared with Sham (Table 1, P=0.03 for both). Body weight and plasma renin activity (PRA) were not significantly different among the groups, but serum creatinine (Scr) was elevated in CAS, HT and CAS+HT (Table 1, P<0.04 each), affected by both CAS and HT. Urinary protein, affected by HT, increased significantly only in CAS+HT compared to Sham and CAS (Table 1, P=0.006 and P=0.045, respectively). Circulating PGF2-α isoprostane levels increased in CAS and CAS+HT compared to Sham and HT (Figure 1A, P<0.05 each), while systemic transforming growth-factor (TGF)-β1 levels increased by HT in HT and CAS+HT (Figure 1B, P=0.02 and P=0.03 vs. Sham, respectively). Norepinephrine levels were slightly reduced in CAS only compared to HT. Systemic levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL10, IL12, IL18 and tumor necrosis factor (TNF)-α were not significantly different among the four groups (Table 1s, P>0.05 for all).


Experimental coronary artery stenosis accelerates kidney damage in renovascular hypertensive swine.

Sun D, Eirin A, Zhu XY, Zhang X, Crane JA, Woollard JR, Lerman A, Lerman LO - Kidney Int. (2014)

Systemic, cardiac, and renal characteristics in Sham, hypertension (HT), coronary artery stenosis (CAS), and CAS+HT pigs. A. Circulating PGF2-α isoprostane. B. Systemic transforming growth-factor (TGF)-β1. C-D. Representative cardiac CT images obtained at the middle left-ventricle (LV). In hypertensive animals (HT and CAS+HT), the LV wall is thickened. The arrow in C shows myocardial lateral wall thinning distal to a high-grade CAS (illustrated in D). E, Cardiac output. F, Myocardial perfusion. G, LV muscle mass (LVMM). H, Glomerular filtration rate (GFR). I, Change in renal blood flow (ΔRBF) in response to acetylcholine (Ach). J, Intratubular concentration (ITC) in the different nephron segments. *P<0.05 vs. Sham; #P<0.05 vs. HT; &P<0.05 vs. CAS.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4382395&req=5

Figure 1: Systemic, cardiac, and renal characteristics in Sham, hypertension (HT), coronary artery stenosis (CAS), and CAS+HT pigs. A. Circulating PGF2-α isoprostane. B. Systemic transforming growth-factor (TGF)-β1. C-D. Representative cardiac CT images obtained at the middle left-ventricle (LV). In hypertensive animals (HT and CAS+HT), the LV wall is thickened. The arrow in C shows myocardial lateral wall thinning distal to a high-grade CAS (illustrated in D). E, Cardiac output. F, Myocardial perfusion. G, LV muscle mass (LVMM). H, Glomerular filtration rate (GFR). I, Change in renal blood flow (ΔRBF) in response to acetylcholine (Ach). J, Intratubular concentration (ITC) in the different nephron segments. *P<0.05 vs. Sham; #P<0.05 vs. HT; &P<0.05 vs. CAS.
Mentions: Renal-artery-stenosis increased mean arterial pressure (MAP) in both HT and CAS+HT compared with Sham (Table 1, P=0.03 for both). Body weight and plasma renin activity (PRA) were not significantly different among the groups, but serum creatinine (Scr) was elevated in CAS, HT and CAS+HT (Table 1, P<0.04 each), affected by both CAS and HT. Urinary protein, affected by HT, increased significantly only in CAS+HT compared to Sham and CAS (Table 1, P=0.006 and P=0.045, respectively). Circulating PGF2-α isoprostane levels increased in CAS and CAS+HT compared to Sham and HT (Figure 1A, P<0.05 each), while systemic transforming growth-factor (TGF)-β1 levels increased by HT in HT and CAS+HT (Figure 1B, P=0.02 and P=0.03 vs. Sham, respectively). Norepinephrine levels were slightly reduced in CAS only compared to HT. Systemic levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1α, IL-1β, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL10, IL12, IL18 and tumor necrosis factor (TNF)-α were not significantly different among the four groups (Table 1s, P>0.05 for all).

Bottom Line: Systemic levels of PGF2-α isoprostane, a marker of oxidative stress, increased in CAS and CAS plus HT, whereas single-kidney blood flow responses to acetylcholine were significantly blunted only in CAS plus HT compared with sham, HT, and CAS, indicating renovascular endothelial dysfunction.Tissue expression of inflammatory and oxidative markers were elevated in the CAS pig kidney, and further magnified in CAS plus HT, whereas angiogenic factor expression was decreased.Bendavia, a mitochondria-targeted peptide, decreased oxidative stress and improved renal function and structure in CAS.

View Article: PubMed Central - PubMed

Affiliation: 1] Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota, USA [2] Department of Nephrology, The Affiliated Hospital of Xuzhou Medical College, Xuzhou, China.

ABSTRACT
The impact of coronary artery stenosis (CAS) on renal injury is unknown. Here we tested whether the existence of CAS, regardless of concurrent atherosclerosis, would induce kidney injury and magnify its susceptibility to damage from coexisting hypertension (HT). Pigs (seven each) were assigned to sham, left-circumflex CAS, renovascular HT, and CAS plus HT groups. Cardiac and nonstenotic kidney functions, circulating and renal inflammatory and oxidative markers, and renal and microvascular remodeling were assessed 10 weeks later. Myocardial perfusion declined distal to CAS. Systemic levels of PGF2-α isoprostane, a marker of oxidative stress, increased in CAS and CAS plus HT, whereas single-kidney blood flow responses to acetylcholine were significantly blunted only in CAS plus HT compared with sham, HT, and CAS, indicating renovascular endothelial dysfunction. Tissue expression of inflammatory and oxidative markers were elevated in the CAS pig kidney, and further magnified in CAS plus HT, whereas angiogenic factor expression was decreased. Bendavia, a mitochondria-targeted peptide, decreased oxidative stress and improved renal function and structure in CAS. Furthermore, CAS and HT synergistically amplified glomerulosclerosis and renal fibrosis. Thus, mild myocardial ischemia, independent of systemic atherosclerosis, induced renal injury, possibly mediated by increased oxidative stress. Superimposed HT aggravates renal inflammation and endothelial dysfunction caused by CAS, and synergistically promotes kidney fibrosis, providing impetus to preserve cardiac integrity in order to protect the kidney.

No MeSH data available.


Related in: MedlinePlus