Study of high uric acid induced hypertension in rats
|School||Beijing Union Medical College|
|Keywords||Hyperuricemia Oxonic acid Hypertension Renin-Angiotensin system MeculaDensa|
BackgroundHypertension is a significant characteristic of cardiorenal epidemic worldwide. Accumulating evidences reveal that hyperuricemia is its independent risk factor while the exact mechanism between them remains unclear. Hypothesis includes uric acid related endothelial dysfunction, salt-sensitivity increase and stimulation of rennin-angiotensin system. To observe the effect of hyperuricemia on rennin regulation and salt-sensitivity using rat model is of very meaningful to the understating of the relationship between hyperuricemia and hypertension.Material and methods1. Mild hyperuricemia was induced in SD rats by providing a uricase inhibitor (oxonic acid) in the diet and also by intra gastic tube feeding later at a dose of750mg/kg/d. Comparison of uric acid levels were done between different conditions of blood withdrawal.2. Blood pressure was measured by a non-invasive tail-cuff method. Filtration sodium excretion fraction was obtained in the4th week from both hypertensive and normotensive rats.3. Real-time PCR were performed to quantify the relative mRNA level of renal rennin inside well-preserved kidney tissues. mRNA levels of two major components of MD regulation pathway, COX2and neuronal NO synthase were also analyzed.Results1. Normal salt plus2%OA diet with or without OA i.g. both can elevate serum uric acid level modestly. Moreover, the conditions of blood withdrawal may produce a significant difference in uric acid level.2.2%OA diet elevated blood pressure after2weeks, whereas control rats remained normotensive. Filtration sodium excretion fraction didn’t change in early stage when given a normal salt diet.3. Hyperuricemic rats didn’t exhibited an increase in renal rennin mRNA level under normal salt diet. Change of COX2and nNOS mRNA level were not observed either.Conclusions 1.2%OA diet with or without OA i.g. both can elevate uric acid level.2. Hyperuricemia can cause hypertension in rats, while filtration sodium excretion fraction didn’t change under normal salt diet.3. Hyperuricemia is not stimulating rennin release through MD regulation pathways under normal salt diet.