Hyperuricemia attenuates aortic nitric oxide generation, through inhibition of arginine transport, in rats.
Level 5 - mechanism / opinion, no new human data
Animal/preclinical experimental study
PubMed 21099230 · doi:10.1159/000320356
What was done
Experiments were performed using freshly harvested aortas from untreated control rats and oxonic acid-fed hyperuricemic rats. Outcomes were compared across untreated hyperuricemic rats and hyperuricemic rats treated with allopurinol, benzbromarone, or arginine, as well as control rats treated with allopurinol alone. The researchers assessed aortic arginine transport, blood pressure responses to acetylcholine, L-NAME-inhibitable cGMP response to carbamyl-choline, protein nitration, and protein abundance of cationic amino acid transporter-1 (CAT-1), PKCα, and phosphorylated PKCα.
What was found
Arginine transport was significantly decreased in hyperuricemic rats. Benzbromarone and arginine prevented this decrease in hyperuricemic rats, whereas allopurinol did not. Arginine transport was also significantly decreased in normouricemic control rats treated with allopurinol. The blood pressure response to acetylcholine was significantly attenuated in hyperuricemic rats, an effect prevented in all treatment groups. The L-NAME-inhibitable cGMP response to carbamyl-choline was significantly decreased in hyperuricemia; this was completely prevented by benzbromarone and arginine, and partially prevented by allopurinol. Hyperuricemia significantly increased protein nitration, which was prevented by all three treatments. Total protein levels of CAT-1, PKCα, and phosphorylated PKCα remained unchanged across all groups. No exact numeric values or sample sizes were reported in the abstract.
Why it matters
This study provides mechanistic evidence that hyperuricemia-induced endothelial dysfunction stems primarily from attenuated CAT-1-mediated arginine transport rather than reduced transporter protein expression. It also highlights differential direct effects of urate-lowering agents, showing that allopurinol impaired arginine uptake in control vessels while benzbromarone preserved it.
Limits
Findings are limited to an ex vivo rodent model of chemically induced hyperuricemia, which may not directly translate to chronic human vascular pathology. The abstract does not provide sample sizes (n), treatment dosages, durations, or numerical effect sizes and confidence intervals.
Cited by
- supports Uric acid directly impairs endothelial nitric oxide levels through arginine transport inhibition, enzyme inhibition, and direct scavenging or binding.