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(Hypertension. 1997;29:408.)
© 1997 American Heart Association, Inc.

State-of-the-Art-Lecture

Regulation of Growth of the Adrenal Gland in DOC-Salt Hypertension

Role of Angiotensin II Receptor Subtypes

Fernando Elijovich; Hua-Wei Zhao; Cheryl L. Laffer; Yong Du; Donald J. DiPette; Tadashi Inagami; Donna H. Wang

From the Department of Internal Medicine, University of Texas Medical Branch (Galveston), and the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tenn (T.I.).

Correspondence to Fernando Elijovich, MD, 2-26 Former Shriners Burns Institute, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0829. E-mail felijovi{at}impol.utmb.edu

To investigate the role of the renin-angiotensin system in the regulation of adrenal growth in deoxycorticosterone (DOC)-salt hypertensive rats, and the adrenal gene expression of angiotensin AT₁ and AT₂ receptors, three groups of uninephrectomized rats+DOC pellet+0.9% NaCl were given water (DOC), losartan (DOC-L), or ramipril (DOC-R) by gavage. Controls had sham surgery and water gavage. Tail-cuff systolic and mean intra-arterial blood pressures were significantly higher in the three DOC groups than in controls and not different among the groups. Adrenal weight of DOC was slightly but not significantly greater than that of controls, while those of DOC-L and DOC-R were greater than that of controls (P<.01). Northern blots showed that AT₁ and AT₂ gene expression was significantly reduced in DOC (by 33% and 60%), while that of AT₁ (but not AT₂) was significantly reduced further (versus control and DOC) in DOC-L and DOC-R. There were negative correlations between adrenal weight and AT₁ (r=-.80, P<.0001) or AT₂ (r=-.60, P<.005). We conclude that DOC-salt hypertension downregulates adrenal AT₁ and AT₂ gene expression by different mechanisms. Removal of the effects of angiotensin by losartan or ramipril downregulates AT₁ further and promotes adrenal growth, indicating the presence of an AT₁-mediated growth-inhibitory action of angiotensin II on the adrenal gland. These observations constitute an additional example of a growth-inhibitory role for the AT₁ receptor, opposite to its more common growth-promoting actions in other organs and tissues.

Key Words: receptors, angiotensin II • gene expression regulation • blotting, Northern • losartan • ramipril • deoxycorticosterone • rats

Abbreviations: AT₁, AT₂ = angiotensin receptor subtype 1, 2 • DOC = deoxycorticosterone • GRE = glucocorticoid responsive element • MAP = mean arterial pressure

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