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New Findings: What is the central question of this study?What is the role of the renal nerves in the development of obesity, hyperlipidaemia and hypertension during the long‐term feeding of a moderately high‐fat diet in male obesity‐prone rats?What is the main finding and its importance?The renal nerves play a prominent mediatory role, without influencing the establishment of visceral adiposity and atherogenic hyperlipidaemia, in the induction and progression of pressure natriuresis impairment and hypertension during the developmental period of diet‐induced obesity. Feeding a moderately high‐fat (MHF) diet in male Sprague–Dawley rats induces obesity, pressure natriuresis impairment and hypertension. This study investigated the role of the renal nerves in the impaired pressure natriuresis and hypertension caused by feeding a MHF diet. After collecting baseline data on day 0, 12 rats remained on a low‐fat diet (LF group) while the others were switched onto a MHF diet and diverged into obesity‐resistant (OR) or obesity‐prone (OP). After 4 weeks, half of the OR and OP rats underwent bilateral renal denervation (BRD) to generate four groups: OR, OR/BRD, OP and OP/BRD (n = 12). During 10 weeks, body weight, obesity index, systolic pressure and renal excretory function were measured regularly. After 10 weeks, renal excretory responses to acute salt loading and renal autoregulation were evaluated. The OP and OP/BRD groups had greater increases of body weight and obesity index during the dietary period compared to the other groups, and by week 10 their body weight (425.1 ± 7.2 and 411.9 ± 5.1 g) became considerably larger than that of the LF group (358.5 ± 6.2 g). Renal sodium excretion was reduced by ∼20% at week 4 in the OP and OP/BRD groups, while only the OP group had lower sodium excretion at weeks 6–8 and higher systolic pressure over weeks 5–10 than the other groups and its week 10 systolic pressure reached 138.1 ± 6.7 versus 123.6 ± 2.7 mmHg of the LF group. The OP group showed delayed renal excretory responses to salt loading with rightward and downward shifts in renal autoregulatory curves. Therefore, the renal nerves exert a main mediatory role in the development of pressure natriuresis impairment and hypertension as obesity is established due to the long‐term consumption of the MHF diet in male OP rats. [ABSTRACT FROM AUTHOR]