Effects of oxonic acid-induced hyperuricemia on mesenteric artery tone and cardiac load in experimental renal insufficiency

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.

Hyperuricemia is Associated with Increased Apo AI Fractional Catabolic Rates and Dysfunctional HDL in New Zealand Rabbits

“…ANOVA, *P < 0.05 vs. HDL before treatment, † P < 0.05 vs. aorta rings in the absence of HDL the metabolic pathway of uric acid synthesis includes the activity of xanthine oxidase that produces two equivalents of H 2 O 2 per molecule of uric acid formed. However, it should be emphasized that hyperuricemia in our animal model was not the result of an enhanced synthesis of uric acid, but the result of inhibition of its degradation to allantoin [17,18]. Consequently, oxidative stress derived from enhanced xanthine oxidase activity should not increase in this model of hyperuricemia.…”

“…In fact, Fig. However, it should be emphasized that hyperuricemia in our animal model was not the result of an enhanced synthesis of uric acid, but the result of inhibition of its degradation to allantoin [17,18]. Effect of HDL isolated from rabbits before (black circles) and after OA treatment (open circles) of precontracted rings by 3 × 10 −4 M phenylephrine.…”

“…In this context, oxonic acid (OA) is an uricase inhibitor that has been used to induce hyperuricemia in rats [17,18]. In this context, oxonic acid (OA) is an uricase inhibitor that has been used to induce hyperuricemia in rats [17,18].…”

“…As a consequence, a model of HU independent of the usual concurrent risk factors of CAD is imperative. In this context, oxonic acid (OA) is an uricase inhibitor that has been used to induce hyperuricemia in rats [17,18]. However, the lipoprotein metabolism in rats and humans is very different, and the rabbit is as a better model to understand HDL metabolism [11,14,15].…”

Unfavorable Reduction in the Ratio of Endothelin B to A Receptors in Experimental 5/6 Nephrectomy and Adenine Models of Chronic Renal Insufficiency

“…The groups and the animal numbers were Sham (n=12), Sham+Oxo (n=12), NX (12) and NX+Oxo (n=12). We previously published the study protocol in more detail, and essential demographic and laboratory results of the study groups were included in the previous reports [30][31][32].…”