Abstract
BackgroundRecent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). However, uric acid also functions as an antioxidant with possible beneficial effects.MethodsWe investigated the influence of hyperuricemia on mesenteric arterial tone (main and second order branch) and morphology in experimental CRI. Forty-four Sprague–Dawley rats were 5/6 nephrectomized (NX) or Sham-operated and fed 2.0% oxonic acid or control diet for 9 weeks.ResultsOxonic acid feeding elevated plasma uric acid levels 2.4 and 3.6-fold in the NX and Sham groups, respectively. Plasma creatinine and urea were elevated 2-fold and blood pressure increased by 10 mmHg in NX rats, while hyperuricemia did not significantly influence these variables. Right and left ventricular weight, and atrial and B-type natriuretic peptide mRNA content were increased in NX rats, but were not affected by hyperuricemia. In the mesenteric artery, hyperuricemia did not influence vasoconstrictor responses in vitro to norepinephrine or potassium chloride. The small arteries of NX rats featured hypertrophic remodeling independent of uric acid levels: wall to lumen ratio, wall thickness and cross-sectional area were increased without changes in lumen diameter. In the main branch, vasorelaxations to acetylcholine were impaired in NX rats, but were not affected by hyperuricemia. In contrast, relaxations to the large-conductance Ca2+-activated K+-channel (BKCa) opener NS-1619 were reduced by oxonic acid feeding, whereas responses to nitroprusside were not affected.ConclusionsExperimental hyperuricemia did not influence cardiac load or vascular remodeling, but impaired BKCa -mediated vasorelaxation in experimental CRI.
Highlights
Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI)
Our findings suggest that oxonic acid diet impaired relaxation via Ca2+-activated K+-channel (BKCa) in arterial smooth muscle, but did not significantly affect the endotheliumdependent responses, resistance artery structure, or cardiac load in experimental CRI
Body weight, and heart weight Systolic blood pressure (BP) did not differ in the study groups at the beginning of the oxonic acid diet (Table 1)
Summary
Recent studies suggest a causal role for increased plasma uric acid in the progression of chronic renal insufficiency (CRI). The prevalence of increased plasma uric acid (UA), hyperuricemia, is high in patients with chronic renal insufficiency (CRI). UA has been associated with stimulation of the renal renin-angiotensin system (RAS) and reduced nitric oxide (NO) synthesis. These mechanisms may have participated in the subsequent hypertrophic remodeling of the preglomerular arteries, tubulointerstitial damage, and predisposed to enhanced sodium retention [4,5,6,8]. Incubation of the rat aortic rings with UA was found to reduce vasodilatation in response to acetylcholine (Ach) [9], while the endothelial NO production in vitro was
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