CHANGES IN RENAL ANGIOTENSIN-II RECEPTORS IN SPONTANEOUSLY HYPERTENSIVE RATS BY EARLY TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CAPTOPRIL
Jn. Wu et al., CHANGES IN RENAL ANGIOTENSIN-II RECEPTORS IN SPONTANEOUSLY HYPERTENSIVE RATS BY EARLY TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CAPTOPRIL, Hypertension, 23(6), 1994, pp. 819-822
We tested the hypothesis that in utero treatment with the angiotensin-
converting enzyme inhibitor captopril could change the affinity, densi
ty, and/or subtypes of angiotensin II (Ang II) receptors in the kidney
s 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 b
reeders 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 rece
ptors were determined using radioligand binding techniques and recepto
r antagonists specific for Ang II receptor subtypes 1 and 2 (losartan,
an AT(1)-specific antagonist, and CGP 42112B, an AT(2)-specific antag
onist). AT(1) receptor density in kidneys was higher than AT(2) recept
or 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 An
g II receptor densities in kidneys than other rat groups because of si
gnificantly greater densities of both AT(1) and AT(2) receptors. At 4
months of age, there were no significant differences in Ang II recepto
r densities in kidneys between captopril-treated and control SHR. Our
data indicate that the expression of AT(1) and AT(2) receptors in kidn
eys 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 treat
ment may play a role in the prevention of hypertension in this model.