The role of the adrenal gland in hypertensive transgenic rat TGR(mREN2)27.
The TGR(mREN2)27 is a new monogenetic rat model in hypertension research. As the mouse Ren-2d renin gene is integrated into their genome, they develop fulminant hypertension between 5 and 15 weeks of age, with blood pressure maxima of 300 mm Hg. Their plasma renin-angiotensin system (RAS) is suppressed, but the transgene is highly expressed in the adrenal gland, so we investigated its possible role in steroid metabolism and the pathogenesis of hypertension. During the phase of hypertension development (between 6-18 weeks), the urinary excretion of deoxycorticosterone (DOC), corticosterone (B), 18-hydroxycorticosterone, and aldosterone is 1.5- to 2.5-fold elevated compared with that in Sprague-Dawley (SD) rats (P less than 0.0005) despite the suppressed plasma RAS. Moreover, the adrenal gland in TGR(mREN2)27 shows an increased maximal response to ACTH stimulation in regard to urinary excretion of DOC (after ACTH, 244 +/- 42 ng/24 h in TGR; 62 +/- 10 ng/24 h in SD; P less than 0.0005) and B (after ACTH, 5144 +/- 346 ng/24 h in TGR; 2607 +/- 324 ng/24 h in SD; P less than 0.0005). Additionally, plasma prorenin in TGR was stimulated more than 10-fold, indicating transgene regulation by ACTH. Since spironolactone treatment did not lower the blood pressure in TGR, hypertension solely due to hypermineralocorticoism is unlikely. Our results indicate that the adrenal steroid metabolism is markedly stimulated in young TGR, and the absolute increase in urinary DOC and B after ACTH injections is enhanced, possibly due to a stimulated local intraadrenal RAS.
Sander
M
M
German Institute for High Blood Pressure Research, Max Delbrück Centre for Molecular Medicine, Berlin-Buch.
Bader
M
M
Djavidani
B
B
Maser-Gluth
C
C
Vecsei
P
P
Mullins
J
J
Ganten
D
D
Peters
J
J
D015069:18-Hydroxycorticosterone; D000311:Adrenal Glands / Q000503:physiopathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000652:urine; D000818:Animals; D030801:Animals, Genetically Modified; D003345:Corticosterone / Q000652:urine; D003900:Desoxycorticosterone / Q000652:urine; D004792:Enzyme Precursors / Q000097:blood; D015870:Gene Expression; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood / Q000235:genetics*; D013148:Spironolactone / Q000494:pharmacology
D004792:Enzyme Precursors; D013148:Spironolactone; D003900:Desoxycorticosterone; D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D003345:Corticosterone