Chronic treatment with amlodipine modulates adrenocortical angiotensin II receptors in spontaneously hypertensive rats

We investigated the effects of long-term treatment with calcium-antagonist, amlodipine, on angiotensin II receptors in the adrenal cortex of spontaneo usly hypertensive rats (SHR). Seven-week-old male SHR were treated with ora l amlodipine (10 mg/kg/day) or vehicle (saline) for four weeks. Age-matched normotensive Wistar-Kyoto (WKY) rats were treated with the vehicle similar to control SHR. Systolic blood pressure (SBP) showed time-dependent increa se in SHR but not in WKY rats, while amlodipine treatment significantly red uced the high SEP in SHR, Plasma renin activity was serially increased in S HR, which was further enhanced by amlodipine treatment, But the plasma aldo sterone level which was increased in SHR was not changed by amlodipine. Com petitive reverse transcriptase-polymerase chain reaction showed that the le vel of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressiv ely decreased in vehicle-treated SHR compared to WKY rats and that 4-week c ourse of amlodipine treatment significantly increased AT1R mRNA in SHR to l evels comparable to those in WKY rats. Amlodipine treatment reduced the lev el of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates b oth adrenocortical AT1R and AT2R in SHR in a possibly direct manner, (C) 20 01 Elsevier Science Inc. All rights reserved.