Abstract 16558: Endothelial Cell Transfusion Protects Against Chronic Kidney Disease-Induced Endothelial Dysfunction in Nephrectomized Rats
Introduction: Chronic kidney disease (CKD) is associated with increased cardiovascular morbidity and mortality. We studied whether transfusion of endothelial cells (ECs) 6 wks after 5/6 nephrectomy (Nx) protects against endothelial dysfunction in small (mesenteric, MA), intermediate (renal, RA), and conduit (carotid, CA) arteries.
Methods and Results: Male Sprague-Dawley rats (11 wk) underwent sham surgery vs. Nx. Six wks after Nx, rats were transfused IV with 1.5x106 rat aortic ECs or vehicle and euthanized 1 wk later. Vascular relaxation was assessed by mounting a first-order MA, a second-order RA, and a CA on a myograph. In MAs, acetylcholine (ACh)-induced endothelium-dependent (sensitivity to 10-9-10-5 M ACh, pEC50, Fig A) and endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxations (in response to 10µM Ach, Fig B) were impaired after Nx but normalized with EC transfusion. In RAs, ACh-induced relaxation was impaired after Nx but improved with EC transfusion (Fig C). In CAs, ACh-mediated relaxation was not affected by Nx. Incubation of CAs with inhibitors to nitric oxide synthase (Nω-L-nitro-arginine methylester, L-NAME, 100µM), cyclooxygenase (indomethacin, 10µM), and guanylyl cyclase (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one, ODQ, 10µM) resulted in an increase in basal tension that was significantly reduced by Nx but normalized by EC transfusion (Fig D). This provided indirect evidence that EC transfusion restored basal nitric oxide levels that were reduced after Nx.
Conclusion: CKD in rats leads to abnormal vascular relaxation in small and intermediate arteries and reduced basal levels of nitric oxide in conduit arteries. EC transfusion normalized these vascular dysfunctions indicating that this novel cell therapy may provide a therapeutic strategy for the treatment of CKD-induced vascular dysfunction.
- © 2011 by American Heart Association, Inc.