Increased expression of vascular angiotensin II type 1A receptor gene in glucocorticoid-induced hypertension.
OBJECTIVE
We recently demonstrated that glucocorticoid increases the number of angiotensin II type 1 (AT1) receptors and their gene expression in cultured vascular smooth muscle cells. To clarify whether this mechanism participates in glucocorticoid-induced hypertension, we investigated the effect of dexamethasone on the modulation of vascular AT1 receptor messenger RNA (mRNA) expression in rats.


METHODS
The effects were studied of administering dexamethasone orally to rats at a dose of 0.1 mg/day on the modulation of the expression of vascular AT1 receptor mRNA and the blood pressure. The effects of enalapril maleate, an angiotensin converting enzyme inhibitor, were also evaluated.


RESULTS
The dexamethasone-treated rats showed a rise in systolic blood pressure beginning on day 3. On day 5 the blood pressure rose significantly. Before dexamethasone administration the vascular AT1 receptor mRNA was difficult to detect by Northern blot analysis. However, the level of vascular AT1A receptor mRNA began to increase on day 2, when the blood pressure was not yet elevated, and increased further on day 5. The concurrent administration of dexamethasone and enalapril maleate attenuated the elevation of blood pressure. However, as in the dexamethasone-treated rats, the level of AT1A receptor mRNA began to increase on day 2 and increased further on day 5. In rats treated with enalapril maleate alone, the AT1 receptor mRNA was difficult to detect during the experiment.


CONCLUSIONS
Glucocorticoid increased the amount of vascular AT1 receptor mRNA and contributed to the elevation of blood pressure.
Sato
A
A
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Suzuki
H
H
Nakazato
Y
Y
Shibata
H
H
Inagami
T
T
Saruta
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000235:genetics*; D013599:Systole
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D004656:Enalapril; D003907:Dexamethasone