Increased adrenal renin in transgenic hypertensive rats, TGR(mREN2)27, and its regulation by cAMP, angiotensin II, and calcium.
The newly established rat strain TGR(mREN2)27 is a monogenetic model in hypertension research. Microinjecting the mouse Ren-2d renin gene caused it to become a stable part of the genome. The rats are characterized by fulminant hypertension, low plasma active renin, suppressed kidney renin, high plasma inactive renin, and high extrarenal transgene expression, most prominently in the adrenal cortex. Additionally, they exhibit significantly enhanced excretion of corticosteroids. Here we demonstrate that part of the plasma renin and most of the adrenal renin are transgene determined and that the adrenal renin is strongly activated. TGR(mREN2)27 adrenal cells may serve as a new tool to investigate the regulation and processing of Ren-2d-derived renin and its significance in hypertension and steroid metabolism. Adrenal renin in TGR(mREN2)27 is stimulated by 8-bromo-cAMP (8-Br-cAMP), angiotensin II (ANGII), and calcium. 8-Br-cAMP significantly stimulates active renin and prorenin release, as well as Ren-2d mRNA. Interestingly, within 60 min 8-Br-cAMP, ANGII, and calcimycin stimulate active renin, but not prorenin release. This indicates different intracellular pathways. An activated adrenal renin-angiotensin system in TGR (mREN2)27 as well as the lack of negative feedback on renin secretion by ANGII may be of pathophysiological significance in this hypertensive model.
Department of Pharmacology, University of Heidelberg, Germany.
J
J
Peters
K
K
Münter
M
M
Bader
E
E
Hackenthal
J J
JJ
Mullins
D
D
Ganten
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000201:enzymology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000502:physiology*; D004195:Disease Models, Animal; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics* / Q000378:metabolism*
D004792:Enzyme Precursors; D012333:RNA, Messenger; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D000242:Cyclic AMP; D012083:Renin; D002118:Calcium