RESUMO
The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin-angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose, and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease.
Assuntos
Hipertensão/sangue , Ácido Úrico/sangue , Animais , Ensaios Clínicos como Assunto , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/etiologia , Análise da Randomização Mendeliana , Uricosúricos/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Current evidence supports the role of soluble uric acid as a true mediator of injury, exerting its effects through the induction of growth factors, cytokines, hormones and autacoids. In the present review, we summarize recent studies on the mechanisms involved in the uric acid deleterious effects. RECENT FINDINGS: Although uric acid is considered an antioxidant in plasma, recent clinical and epidemiological studies have found that hyperuricemia is associated with mortality and development of hypertension, cardiovascular and chronic renal diseases. Experimental studies suggest that uric acid induce its detrimental effects at the cellular level entering to vascular smooth muscle cells (VSMC) via an organic anion transport system, and followed by the activation of specific MAP kinases, nuclear transcription factors, with stimulation of COX-2, PDGF A and C chain, PDGF alpha receptor, and various inflammatory mediators, including C-reactive protein and monocyte chemoattractant protein-1. Physiologically, these effects translate into a rise of arterial pressure, VSMC hypertrophy, tubulointerstitial infiltration and glomerular hypertension in the setting of renal vasoconstriction. Uric acid also promotes endothelial dysfunction through inactivation of NO and arresting the proliferation of endothelial cells. Thus, arteriosclerosis induced by hyperuricemia may be a novel mechanism for the development of essential hypertension. SUMMARY: Soluble uric acid has important biologic roles. While it acts as an antioxidant, there is also evidence that uric acid has pro-inflammatory and proliferative effects on VSMC, and causes dysfunction of endothelial cells. These cellular mechanisms may translate into why uric acid is associated with renal and cardiovascular disease.