Objective This study aimed to determine whether the alteration of the pressure natriuresis seen in Lyon genetically hypertensive (LH) rats occurs early, and the possible involvement in this alteration of the most important extra-renal factors that influence natriuresis. Methods In LH rats and their normotensive (LL) controls, acute pressure natriuresis was studied in denervated kidneys with or without controlling extra-renal influence; that is, adrenalectomy and an intravenous infusion of vasopressin, norepinephrine, hydrocortisone and aldosterone. Results With controlling the cited extra-renal influence, LH rats already exhibited, at 5 weeks of age, a slightly higher blood pressure (+9%) and a markedly reduced renal blood flow (-33%) compared with LL rats; their pressure–diuresis and pressure–natriuresis curves were significantly blunted. Between 16 and 50 weeks of age, although BP levels did not change, renal blood flow and glomerular filtration rate declined in LH rats while their pressure–diuresis and pressure–natriuresis curves continued to shift to higher pressures. When studied without controlling extrarenal influence, the values of pressure diuresis and natriuresis were significantly higher than in controlled conditions both in LH and LL rats. However, in 16-week-old rats, the LH/LL ratios for sodium and water excretion remained close under the two experimental conditions. Conclusions The pressure–natriuresis function in LH rat shows early impairment and aggravates with age. This alteration is observed with, as well as without, controlling the influence of the main extra-renal factors that affect natriuresis.