La denervación bilateral renal es insuficiente para prevenir la hipertensión y las complicaciones renales en un modelo murino de dieta alta en grasa

Abstract

One of the hallmarks of metabolic syndrome is the increased renal sympathetic nerve activity, which contributes to hypertension and leads to chronic kidney disease. Clinical evidence and animal models of this condition have shown that renal sympathetic denervation transiently attenuates hypertension while renal injury worsens. Leptin and insulin resistance and other alterations of energy homeostasis play a role in metabolic syndrome's cardiovascular and renal complications. To investigate this issue, we compared the metabolic, cardiovascular, and renal health of male rats that underwent bilateral renal denervation and were fed either with a standard or a high-fat diet for 8 and 12 weeks. The results indicate that the animals fed with hypercaloric diet does not affect the amount of noradrenaline in the kidneys but display increased blood pressure and plasma levels of angiotensin II, proteinuria, decreased glomerular filtration rate, urinary flow, and potassium excretion independently from the surgery. Nevertheless, bilateral renal denervation attenuates the ketonuria observed in intact, high-fat diet-fed rats. The comparison of intracellular proteins in the kidney, downstream of angiotensin II, leptin, and insulin signaling (AKT, PI3K, and ERK1/2) in the kidney showed a combined effect of the renal sympathetic input, the energy content of the diet and time, especially in the long term. Based on of these results, we suggest that renal sympathetic nerve activity plays a role in the early-intermediate stages of the metabolic syndrome. At the same time, the effects of chronic, long-term exposure to the hypercaloric diet prevails on the autonomic regulation of kidney homeostasis.