The Milan hypertensive strain of rats (MHS) is characterized in the prehypertensive phase (4 weeks of age) by a significantly faster bumetanide-sensitive cell membrane Na+,K+,Cl(-)-cotransport as compared to matched normotensive controls (MNS). The isolated kidney preparation, which allows the study of renal function under controlled in vitro conditions, was chosen to compare the natriuretic effect of the loop diuretic, bumetanide, to that of two other diuretics (amiloride and hydrocholorothiazide) acting on different parts of the nephron. Concentrations ranging from 10(-7) to 10(-4) M were tested in 4-week-old MHS and MNS. Our results showed that the natriuretic response to all diuretics was greater in MHS as compared to MNS when evaluated as absolute Na+ excretion (UNA+); this is likely because of the faster basal glomerular filtration rate (GFR) in the hypertensive strain (874 +/- 126 in MHS vs. 556 +/- 33 microliters.min-1.g-1 k wt in MNS, P less than 0.05). However, when calculated either as a difference from basal values (delta UNa+), or per ml of glomerular filtration rate, the response of MHS kidneys to amiloride and hydrochlorothiazide was similar in the two strains: delta UNa+ after amiloride at (10(-4) M was + 2.1 +/- 0.7 in MHS versus + 1.2 +/- 0.2 mumol.g-1.g-1 k wt in MNS; after hydrochlorothiazide 10(-4) M it was + 1.7 +/- 0.9 in MHS versus + 1.1 +/- 0.4 mumol.min-1.g-1 k wt in MNS, values not statistically different.(ABSTRACT TRUNCATED AT 250 WORDS)