Effects of angiotensin I converting enzyme (ACE)-related substances on prostacyclin generation and ACE activity of human vascular endothelial cells and rat aortic rings.
The effects of angiotensin I (ANG I) converting enzyme (ACE)-related substances on prostacyclin (PGI2) generation were investigated using cultured human vascular endothelial cells (EC) and rat aortic rings. ANG I or bradykinin (BK) increased while captopril decreased PGI2 generation and ACE activity of EC, whereas ANG II was without effect. The enhancement of PGI2 generation induced by ANG I or BK was not affected by the pretreatment with captopril. In rat aortic rings, ANG I, ANG II, and BK enhanced whereas captopril (10(-3) M) attenuated PGI2 generation. Mechanical stimulation of aortic rings stimulated PGI2 generation. These results suggest that (a) the conversion of ANG I to ANG II did not enhance PGI2 generation in EC; (b) the ANG II stimulated PGI2 generation of aortic rings was partially derived by mechanical stimulation of EC, probably originating from the contraction of smooth muscle cells by ANG II; (c) captopril directly inhibited PGI2 generation; and (d) in EC, the stimulation of PGI2 generation by ANG I or BK is probably regulated by an 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
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D002216:Captopril / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY
D002216:Captopril; D011464:Epoprostenol; D007703:Peptidyl-Dipeptidase A