Comparison of the effects of renal denervation at early or advanced stages of hypertension on cardiac, renal, and adipose tissue pathology in Dahl salt-sensitive rats

Renal denervation (RDN) has emerged as a novel therapy for drug-resistant hypertension. We here examined the effects of RDN at early versus advanced stages of hypertension on blood pressure and organ pathology in rats with salt-sensitive hypertension. Dahl salt-sensitive (DahlS) rats fed an 8% NaCl diet from 6 weeks of age were subjected to RDN (surgical ablation and application of 10% phenol in ethanol) or sham surgery at 7 (early stage) or 9 (advanced stage) weeks and were studied at 12 weeks. RDN at early or advanced stages resulted in a moderate lowering of blood pressure. Although RDN at neither stage affected left ventricular (LV) and cardiomyocyte hypertrophy, it ameliorated LV diastolic dysfunction, fibrosis, and inflammation at both stages. Intervention at both stages also attenuated renal injury as well as downregulated the expression of angiotensinogen and angiotensin-converting enzyme (ACE) genes and angiotensin II type 1 receptor protein in the kidney. Furthermore, RDN at both stages inhibited proinflammatory gene expression in adipose tissue. The early intervention reduced both visceral fat mass and adipocyte size in association with downregulation of angiotensinogen and ACE gene expression. In contrast, the late intervention increased fat mass without affecting adipocyte size as well as attenuated angiotensinogen and ACE gene expression. Our results thus indicate that RDN at early or late stages after salt loading moderately alleviated hypertension and substantially ameliorated cardiac and renal injury and adipose tissue inflammation in DahlS rats. They also suggest that cross talk among the kidney, cardiovascular system, and adipose tissue may contribute to salt-sensitive hypertension.Supposed mechanism for the beneficial effects of RDN on hypertension and target organ damage in DahlS rats. RDN at early or late stages after salt loading moderately alleviated hypertension and substantially ameliorated renal injury in DahlS rats. Cross talk among the kidney, cardiovascular system, and adipose tissue possibly mediated by circulating RAS may contribute to salt-sensitive hypertension. LV; left ventricular, NE; norepinephrine, RAS; renin-angiotensin system, RDN; renal denervation. Supposed mechanism for the beneficial effects of RDN on hypertension and target organ damage in DahlS rats. RDN at early or late stages after salt loading moderately alleviated hypertension and substantially ameliorated renal injury in DahlS rats. Cross talk among the kidney, cardiovascular system, and adipose tissue possibly mediated by circulating RAS may contribute to salt-sensitive hypertension. LV; left ventricular, NE; norepinephrine, RAS; renin-angiotensin system, RDN; renal denervation.