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

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.

• Authors: Dong Sun, Alfonso Eirin, Xiang-Yang Zhu, Xin Zhang, John A Crane, John R Woollard, Amir Lerman, Lilach O Lerman
• Journal: Kidney international (Kidney Int) Vol. 87 Issue 4 Pg. 719-27 (Apr 2015) ISSN: 1523-1755 [Electronic] United States
• PMID: 25337776 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antioxidants
• Oligopeptides
• Transforming Growth Factor beta1
• arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide
• Dinoprost
• Acetylcholine

Topics

• Acetylcholine (pharmacology)
• Acute Kidney Injury (etiology, pathology, physiopathology)
• Animals
• Antioxidants (pharmacology)
• Arterial Pressure
• Coronary Angiography
• Coronary Stenosis (complications, physiopathology)
• Coronary Vessels (diagnostic imaging)
• Dinoprost (blood)
• Endothelium (physiopathology)
• Female
• Fibrosis
• Glomerular Filtration Rate
• Hypertension, Renovascular (complications, physiopathology)
• Kidney (blood supply, pathology)
• Oligopeptides (pharmacology)
• Oxidative Stress (drug effects)
• Renal Circulation (drug effects)
• Stroke Volume
• Swine
• Transforming Growth Factor beta1 (blood)