ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension.
Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.
Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 367, Paris, France.
J F
JF
Arnal
T
T
Battle
C
C
Rasetti
M
M
Challah
O
O
Costerousse
E
E
Vicaut
J B
JB
Michel
F
F
Alhenc-Gelas
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D001483:Base Sequence; D001794:Blood Pressure; D015153:Blotting, Western; D002250:Carbon Radioisotopes; D017931:DNA Primers; D015773:Enalaprilat / Q000494:pharmacology; D015870:Gene Expression; D006978:Hypertension, Renovascular / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D016376:Oligonucleotides, Antisense; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values
D002250:Carbon Radioisotopes; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; D015773:Enalaprilat