Feedback regulation of angiotensin converting enzyme activity and mRNA levels by angiotensin II.
Although renin and angiotensinogen are known to be subject to feedback regulation, the effects of angiotensin II (Ang II) on the regulation of angiotensin converting enzyme (ACE) gene expression and enzymatic activity have not yet been studied. Therefore, the effects of exogenous Ang II infusion and ACE inhibition on ACE mRNA expression were examined. Ang II was infused intravenously in male Sprague-Dawley rats for 3 days at 100 (low dose), 300 (medium dose), or 1,000 (high dose) ng/kg per minute (n = 8 for each group). Compared with control (vehicle infusion, n = 8), Ang II infusion increased plasma Ang II concentration (62, 101, 126 [p < 0.05], and 187 [p < 0.05] fmol/ml) and mean arterial blood pressure (106, 119 [p < 0.05], 134 [p < 0.05], and 125 mm Hg for control, low, medium, and high doses, respectively). Ang II infusion decreased ACE mRNA levels in the lung (57%, 52%, and 51%; p < 0.05 for each) and testis (49%, 63%, and 53% of control for low, medium, and high doses, respectively; p < 0.05 for each), two major sites of ACE synthesis. There was, albeit less pronounced, a parallel decrease in pulmonary ACE activity (4.38, 3.92, 3.07 [p < 0.05], and 3.48 [p < 0.05] nM/mg per minute for control, medium, and high doses, respectively). In contrast, serum (54, 50, 48, and 38 [p < 0.05] nM/ml per minute) and testicular (2.63, 2.08 [p < 0.05], 2.24, and 2.18 nM/mg per minute for control, low, medium, and high doses, respectively) ACE activities displayed only minimal change in animals infused with Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
Schunkert
H
H
Falk Cardiovascular Research Center, Stanford, Calif.
Ingelfinger
J R
JR
Hirsch
A T
AT
Pinto
Y
Y
Remme
W J
WJ
Jacob
H
H
Dzau
V J
VJ
D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001669:Biochemical Phenomena; D001671:Biochemistry; D001794:Blood Pressure; D015152:Blotting, Northern; D005246:Feedback; D007262:Infusions, Intravenous; D008168:Lung / Q000201:enzymology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000201:enzymology
D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A