[The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems].
The effects of hypotensive agents (captopril, enalaprilate, and lisinopril) on the activities of components of the fibrinolytic system (FS) and the effects of antifibrinolytic agents (6-aminohexanoic acid (6-AHA) and tranexamic acid (t-AMCHA)) on the activities of angiotensin converting enzyme (ACE) were studied in vitro. Enalaprilate did not affect the FS activity. Captopril considerably inhibited the amidase activities of urokinase (u-PA), plasminogen tissue activator (t-PA), and plasmin ([I]50 (2.0-2.6) +/- 0.1 mM), and the activation of Glu-plasminogen affected by t-PA and u-PA ([I]50 (1.50-1.80) +/- 0.06 mM), which may be due to the presence of a mercapto group in the inhibitor molecule. Lisinopril did not affect the amidase activities of FS enzymes, but stimulated Glu-plasminogen and u-PA activation and inhibited activation of t-PA-fibrin-bound Glu-plasminogen ([I]50 (12.0 +/- 0.5) mM). Presumably, these effects can be explained by the presence in lisinopril of a Lys side residue, whose binding to lysine-binding Glu-plasminogen centers resulted, on the one hand, in the transformation of its closed conformation to a semi-open one and, on the other hand, in its desorption from fibrin. Unspecific inhibition of the activity of ACE, a key enzyme of the renin-angiotensin system, in the presence of 6-AHA and t-AMCHA ([I]50 10.0 +/- 0.5 and 7.5 +/- 0.4 mM, respectively) was found. A decrease in the ACE activity along with the growth of the fibrin monomer concentration was revealed. The data demonstrate that, along with endogenous mediated interactions, relations based on the direct interactions of exogenous inhibitors of one system affecting the activities of components of another system can take place.
Mukhametova
L I
LI
Gulin
D A
DA
Binevskiĭ
P V
PV
Aĭsina
R B
RB
Kost
O A
OA
Nikol'skaia
I I
II
D015119:Aminocaproic Acid / Q000737:chemistry; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D000933:Antifibrinolytic Agents / Q000737:chemistry*; D002216:Captopril / Q000737:chemistry; D015773:Enalaprilat / Q000737:chemistry; D004789:Enzyme Activation; D005337:Fibrin / Q000737:chemistry; D005341:Fibrinolysin / Q000037:antagonists & inhibitors / Q000737:chemistry; D017706:Lisinopril / Q000737:chemistry; D010958:Plasminogen / Q000737:chemistry; D012083:Renin / Q000737:chemistry; D012084:Renin-Angiotensin System; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000737:chemistry; D014148:Tranexamic Acid / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000737:chemistry
D000806:Angiotensin-Converting Enzyme Inhibitors; D000933:Antifibrinolytic Agents; D014148:Tranexamic Acid; D005337:Fibrin; D010958:Plasminogen; D002216:Captopril; D017706:Lisinopril; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator; D012083:Renin; D015773:Enalaprilat; D015119:Aminocaproic Acid