Converting enzyme inhibition and vascular prostacyclin synthesis: effect of kinin receptor antagonism.
The effects of angiotensin I-converting enzyme (ACE) inhibitors and bradykinin (BK) on prostacyclin (PGI2) production in isolated arterial tissue were investigated. Rings of rat abdominal aorta were incubated in Krebs-Ringer bicarbonate buffer and PGI2 generation was assessed by the determination of its stable hydrolysis product; 6-keto-PGF1 alpha. The addition of both ACE inhibitors, captopril and lisinopril, and bradykinin resulted in dose-dependent stimulation of PGI2 biosynthesis when the individual substance was added into the incubation buffer at final concentrations between 10(-8) and 10(-5) M. The bradykinin-induced stimulation of PGI2 synthesis was dose dependently inhibited by the BK receptor antagonist, D-Arg[Hyp3, Thi5,8, D-Phe7]BK. The captopril- and lisinopril-induced stimulation of vascular 6-keto-PGF1 alpha production was also significantly decreased when the BK antagonist was added to the incubation medium together with the ACE inhibitors. Our results show that both captopril and lisinopril stimulate PGI2 synthesis in arterial tissue and that this effect may be secondary to changes in the activity of the kinin system.
Hoffmann
G
G
Medizinische Universitäts-Poliklinik, Bonn, F.R.G.
Pietsch
R
R
Göbel
B O
BO
Weisser
B
B
Bönner
G
G
Vetter
H
H
Düsing
R
R
D015121:6-Ketoprostaglandin F1 alpha / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D066298:In Vitro Techniques; D017706:Lisinopril; D009130:Muscle, Smooth / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D015777:Eicosanoids; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; C058532:HOE k86-4321; D015121:6-Ketoprostaglandin F1 alpha; D004656:Enalapril; D002216:Captopril; D011464:Epoprostenol; D017706:Lisinopril; D001920:Bradykinin