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 AT1-specific antagonist, and CGP 42112B, an AT2-specific antagonist). AT1 receptor density in kidneys was higher than AT2 receptor density in both neonatal and adult rats. AT1 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 AT1 and AT2 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 AT1 and AT2 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Wu
J N
JN
Department of Physiology and Biophysics, University of Alabama at Birmingham 35294.
Edwards
D
D
Berecek
K H
KH
D000375:Aging / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001667:Binding, Competitive; D002216:Captopril / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D012016:Reference Values
D000806:Angiotensin-Converting Enzyme Inhibitors; D011945:Receptors, Angiotensin; D002216:Captopril