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.