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 spontaneously hypertensive rats (SHR). Seven-week-old male SHR were treated with oral 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 increase in SHR but not in WKY rats, while amlodipine treatment significantly reduced the high SBP in SHR. Plasma renin activity was serially increased in SHR, which was further enhanced by amlodipine treatment. But the plasma aldosterone level which was increased in SHR was not changed by amlodipine. Competitive reverse transcriptase-polymerase chain reaction showed that the level of adrenocortical angiotensin II type 1 receptor (AT1R) mRNA progressively decreased in vehicle-treated SHR compared to WKY rats and that 4-week course of amlodipine treatment significantly increased AT1R mRNA in SHR to levels comparable to those in WKY rats. Amlodipine treatment reduced the level of adrenocortical angiotensin II type 2 receptor (AT2R) mRNA in SHR from 8 weeks of age. Thus, chronic amlodipine treatment differently modulates both adrenocortical AT1R and AT2R in SHR in a possibly direct manner.
Kishida
M
M
Department of Medicine III, Okayama University Medical School, Okayama University, Japan. endocrin@cc.okayama-u.ac.jp
Otsuka
F
F
Ogura
T
T
Kataoka
H
H
Nakamura
Y
Y
Yamauchi
T
T
Takahashi
M
M
Yokota
K
K
Mimura
Y
Y
Makino
H
H
D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D000450:Aldosterone / Q000097:blood; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D012083:Renin / Q000097:blood; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013599:Systole / Q000187:drug effects / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D017311:Amlodipine; D000450:Aldosterone; D012083:Renin