Regulation of the gene expression of type-1 angiotensin II receptor in spontaneously hypertensive rats.
Regulation of the gene expression of type-1 angiotensin II receptor (AT1) by treatment with manidipine, a calcium channel blocker, or delapril, an angiotensin converting enzyme inhibitor, for one week was assessed in the adrenal gland, heart, kidney, and brain from spontaneously hypertensive rats (SHR). Tissue AT1 receptor messenger RNA (mRNA) content was measured by reverse transcriptase-polymerase chain reaction. Treatment with manidipine (3 mg/kg/day) or delapril (30 mg/kg/day) lowered systolic blood pressure (SBP) significantly (p < 0.01) (delta SBP; -73 mmHg or -67 mmHg, respectively). Although delapril markedly increased plasma renin activity (PRA), manidipine did not alter PRA. AT1 receptor mRNA content in the adrenal gland was significantly (p < 0.01) decreased by treatment with manidipine or delapril. In contrast, cardiac AT1 receptor mRNA content was significantly (p < 0.01) increased by treatment with either agent. There was no significant change in renal and brain AT1 receptor mRNA contents. These findings suggest that although the expression of AT1 receptor gene depends on the circulating renin-angiotensin system (RAS), it is regulated independently in a tissue-specific manner via the local RAS in each tissue of SHR.
Kitami
Y
Y
Second Department of Internal Medicine, Ehime University School of Medicine, Japan.
Okura
T
T
Wakamiya
R
R
Marumoto
K
K
Iwata
T
T
Hiwada
K
K
D000311:Adrenal Glands / Q000378:metabolism; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D007189:Indans / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009578:Nitrobenzenes; D010879:Piperazines; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000235:genetics*; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D007189:Indans; D009578:Nitrobenzenes; D010879:Piperazines; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; C054218:manidipine; D012083:Renin; C047759:delapril