CHANGES IN RENAL ANGIOTENSIN-II RECEPTORS IN SPONTANEOUSLY HYPERTENSIVE RATS BY EARLY TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CAPTOPRIL

We tested the hypothesis that in utero treatment with the angiotensin-converting enzyme inhibitor captopril could change the affinity, density, and/or subtypes of angiotensin II (Ang II) receptors in the kidneys of spontaneously hypertensive rats (SHR). Newborn, 7-day-old, and 4-month-old SHR and Wistar-Kyoto (WKY) rats were used. SHR and WKY rat breeders were treated with captopril (0.4 mg/mL, 100 mg/kg per day) in drinking water, and their pups were maintained on captopril treatment until experimentation. Control groups were untreated, age-matched SHR and WKY rats. The density, affinity, and subtypes of renal Ang II receptors were determined using radioligand binding techniques and receptor antagonists specific for Ang II receptor subtypes 1 and 2 (losartan, an AT(1)-specific antagonist, and CGP 42112B, an AT(2)-specific antagonist). AT(1) receptor density in kidneys was higher than AT(2) receptor density in both neonatal and adult rats. AT(1) receptor density in kidneys increased approximately twofold from birth to 7 days of age in all groups. Newborn and 7-day-old SHR showed significantly greater Ang II receptor densities in kidneys than other rat groups because of significantly greater densities of both AT(1) and AT(2) receptors. At 4 months of age, there were no significant differences in Ang II receptor densities in kidneys between captopril-treated and control SHR. Our data indicate that the expression of AT(1) and AT(2) receptors in kidneys is differentially regulated during development. Enhanced activity of the renal renin-Ang II system in newborn and probably fetal SHR may be involved in the pathogenesis of hypertension. The decrease in the density of kidney AT(1) receptors in newborn SHR after captopril treatment may play a role in the prevention of hypertension in this model.