Effects of angiotensin I converting enzyme (ACE) related substances upon the vascular prostacyclin generation.
We investigated the interaction of angiotensin I (AI) converting enzyme (ACE) related substances to prostacyclin (PGI2) generation and ACE activity using cultured human vascular endothelial cells (EC) and rat aortic rings (AR). In case of cultured EC, AI and bradykinin (BK) increased PGI2 generation and at the same time ACE released from EC, however angiotensin II (AII) did not show any effect on both of them. When the EC were pretreated by captopril both of basal PGI2 production and ACE activity were reduced but the enhancing effects on PGI2 generation by AI or BK were preserved. On the other hand in the experimental system with AR, not only AI or BK but also AII increased PGI2 generation and the higher concentration of captopril inhibited PGI2 generation. When the EC were removed, the enhancing effect by AII was diminished and the mechanical stimulation to AR remarkably increased PGI2. From these experimental studies, we obtained the results that (1) the reported hypothesis that the vasodilative effect of captopril would be developed by the enhanced PGI2 generation was not confirmed in our systems of EC and AR. (2) AII did not affect on PGI2 generation of EC. Therefore the enhanced PGI2 generation by AII in AR was considered to be mainly derived from the mechanical stimulation to EC by the AII induced smooth muscle cells contraction. (3) It was speculated that the enhanced PGI2 generation by AI or BK might be modulated through their activating effect on ACE as an autoregulatory mechanism.
Nakagawa
M
M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Sawada
S
S
Uno
M
M
Takamatsu
H
H
Nakamura
Y
Y
Nakanishi
Y
Y
Tsuji
H
H
Toyoda
T
T
Sasaki
S
S
Takeda
K
K
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin