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Dual ETA/B receptor blockade therapy in renovascular disease (692.4)
Author(s) -
Tullos Nathan,
Davidovich Ryan,
Chade Alejandro
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.692.4
Subject(s) - medicine , renal function , blockade , kidney disease , kidney , renal artery stenosis , urology , albuminuria , receptor , endocrinology , endothelin receptor , renal blood flow , renal artery
Renovascular disease (RVD) is a progressive disorder that may progress to chronic kidney disease and end stage renal disease. Endothelin 1 (ET‐1) is potent vasoconstrictor that contributes to normal renal function but may also contribute to renal injury when up‐regulated, mainly via ETA receptors. The majority of renal ET research has focused on the ET‐1/ETA pathway, since the ETB receptor is considered renoprotective. However, little is known about the role of ETB receptors in RVD and in certain pathological situations ETA and B receptors may elicit similar actions. Thus, this study aimed to determine if dual blockade of the ET receptors alters the progression of renal injury in RVD. RVD was induced by unilateral renal artery stenosis in pigs and observed for up to 10 weeks. Pigs were divided (n=5 each) in normal, RVD and RVD daily treated with dual ETA/B receptor blocker (Macitentan, 7.5 mg/day) from week 6 to 10. In vivo single‐kidney renal blood flow (RBF) and filtration (GFR) were measured using computed tomography at 6 weeks and 10 weeks. Pigs were euthanized after 10 weeks and ex vivo studies performed to quantify renal microvascular (MV) density, inflammation and injury. 4 weeks of dual ETA/B blockade in pigs with established RVD improved RBF and MV density, reduced albuminuria, renal inflammatory activity and MV rarefaction (Figure). GFR and creatinine remained unchanged. These preliminary results support the notion that ETB blockade in RVD may not accelerate the progression of renal damage. While a functional ETB receptor may benefit renal function, this study suggests that dual blockade of the ETA/B receptors may attenuate progressive renal injury in chronic RVD.Grant Funding Source : Supported by NIH‐NHLBI (HL095638, PI AR Chade) and T32 Training Grant (T32HL105324, PI J Granger)