TY - JOUR
T1 - Beneficial action of a new angiotensin-converting enzyme inhibitor (SQ 14,225) in hemorrhagic shock in cats
AU - Trachte, G. J.
AU - Lefer, A. M.
PY - 1978
Y1 - 1978
N2 - A new angiotensin-converting enzyme inhibitor (CEI), SQ 14,225, was infused at 0.5 mg/kg per hr, into cats to determine its effect in hemorrhagic shock. Cats were bled to a mean arterial blood pressure (MABP) of 40 mm Hg for 150 minutes; this was followed by reinfusion and a 120-minute postoligemic observation period. Hemorrhage shock and sham shock controls were given an infusion of the CEI or its vehicle (0.9% NaCl). The degree of converting enzyme inhibition was assessed by measuring pressor responses to angiotensin I and II and by radioimmunoassay determination of plasma angiotensin II concentration. In vitro studies on cat papillary muscles and vascular smooth muscle strips revealed no direct inotropic or vasoactive effect of SQ 14,225. Nevertheless, hemorrhaged cats given the CEI demonstrated a significantly higher final arterial pressure than hemorrhaged cats given NaCl (96 vs. 51 mm Hg) (P < 0.01), indicating a significant prolongation of circulatory stability which is closely related to survival. Circulating lysosomal hydrolase (i.e., cathepsin D) activity (3.5 vs. 11-fold increases) and total plasma proteolysis (25% vs. 100% increases) were significantly reduced in the shocked cats given the CEI compared to the untreated shocked animals. Formation of a myocardial depressant factor (MDF) also was significantly diminished by CEI treatment (26 vs. 62 U). These results indicate that CEI improved the hemodynamic and biochemical status of cats in hemorrhagic shock and suggest that blockade of angiotensin II formation may be beneficial in hemorrhagic shock. Abolition of other actions of converting enzymes (e.g., potentiation of bradykinin action or inhibition or proteolysis) may also be involved in the protective mechanisms.
AB - A new angiotensin-converting enzyme inhibitor (CEI), SQ 14,225, was infused at 0.5 mg/kg per hr, into cats to determine its effect in hemorrhagic shock. Cats were bled to a mean arterial blood pressure (MABP) of 40 mm Hg for 150 minutes; this was followed by reinfusion and a 120-minute postoligemic observation period. Hemorrhage shock and sham shock controls were given an infusion of the CEI or its vehicle (0.9% NaCl). The degree of converting enzyme inhibition was assessed by measuring pressor responses to angiotensin I and II and by radioimmunoassay determination of plasma angiotensin II concentration. In vitro studies on cat papillary muscles and vascular smooth muscle strips revealed no direct inotropic or vasoactive effect of SQ 14,225. Nevertheless, hemorrhaged cats given the CEI demonstrated a significantly higher final arterial pressure than hemorrhaged cats given NaCl (96 vs. 51 mm Hg) (P < 0.01), indicating a significant prolongation of circulatory stability which is closely related to survival. Circulating lysosomal hydrolase (i.e., cathepsin D) activity (3.5 vs. 11-fold increases) and total plasma proteolysis (25% vs. 100% increases) were significantly reduced in the shocked cats given the CEI compared to the untreated shocked animals. Formation of a myocardial depressant factor (MDF) also was significantly diminished by CEI treatment (26 vs. 62 U). These results indicate that CEI improved the hemodynamic and biochemical status of cats in hemorrhagic shock and suggest that blockade of angiotensin II formation may be beneficial in hemorrhagic shock. Abolition of other actions of converting enzymes (e.g., potentiation of bradykinin action or inhibition or proteolysis) may also be involved in the protective mechanisms.
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U2 - 10.1161/01.RES.43.4.576
DO - 10.1161/01.RES.43.4.576
M3 - Article
C2 - 210975
AN - SCOPUS:0018082234
SN - 0009-7330
VL - 43
SP - 576
EP - 582
JO - Circulation research
JF - Circulation research
IS - 4
ER -