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Uric acid acutely triggers renin release and causes glomerular hyperfiltration
Author(s) -
Kang Julie Jung,
Toma Ildiko,
Sipos Arnold,
Bansal Eric,
PetiPeterdi Janos
Publication year - 2007
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.21.5.a502-a
Subject(s) - macula densa , endocrinology , juxtaglomerular apparatus , medicine , chemistry , afferent arterioles , tubuloglomerular feedback , renin–angiotensin system , decompensation , nephron , renal function , uric acid , kidney , blood pressure
Uric acid (UA) is a metabolite of dietary fructose and cellular purine degradation and is one of the main risk factors of cardiovascular disease and hypertension. UA activates the intrarenal renin‐angiotensin system (RAS), but the mechanism is not known. Renin release from the juxtaglomerular apparatus (JGA), the rate‐limiting step of RAS activation, is highly regulated. We hypothesized that UA directly causes JGA renin release. Fluorescence confocal microscopy using quinacrine showed that perfusion of 100 μM UA into in vitro microperfused mouse JGA preparations caused a 36 ± 6% decrease of JGA renin content (n=4, P <0.001). UA caused no acute increases in NO production or calcium signaling in the afferent arteriole or glomerular endothelial cells, evaluated by DAF‐FM and Fluo‐4/Fura red imaging. Quantitative in vivo multiphoton imaging of Munich‐Wistar rat kidneys assessed UA (0.1 mg/kg iv)‐induced changes in kidney function. Hemodynamic changes included an acute 35% increase in single‐nephron glomerular filtration rate (snGFR) from 31 ± 1 to 42 ± 2 nl/min (n=8, P <0.001). Cortical blood flow increased: peritubular capillary red blood cell velocity rose from 6 ± 1 to 13 ± 1 μm/ms (n=10, P <0.001). Blood pressure showed no significant changes. This study showed that hyperuricemia may mimic diabetic hypertension: early hyperfunctionality precedes late failure. Non‐endothelial cells of the JGA, possibly JG or macula densa cells, are involved in UA‐mediated renin release.