Beneficial actions of CP-0127, a novel bradykinin receptor antagonist, in murine traumatic shock.
Publication/Presentation Date
3-1-1994
Abstract
We studied the effects of CP-0127, a novel bradykinin receptor antagonist, in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to Noble-Collip drum trauma developed a shock state characterized by marked hypotension, significant increases in plasma-free amino-nitrogen (8.6 +/- 0.97 vs. 2.3 +/- 0.15 U/ml in control rats) and intestinal myeloperoxidase (MPO) activity (2.7 +/- 0.33 vs. 0.08 +/- 0.03 U/100 mg control rats, intestinal tissue), and a survival time of only 110 +/- 9 min. Moreover, superior mesenteric artery (SMA) rings isolated from rats subjected to traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine (ACh) significantly less than rings isolated from control rats (21 +/- 4 vs. 92 +/- 4%, P < 0.001). Administration of CP-0127 at a dose of 10 mg/kg subcutaneously completely blocked the hypotensive response to 2.5 micrograms/kg bradykinin injected intravenously in sham traumatic shock rats. CP-0127 given immediately posttrauma prolonged survival time to 219 +/- 27 min (P < 0.01) and attenuated the increases in plasma-free amino-nitrogen (3.7 +/- 0.41 U/ml, P < 0.01) and tissue MPO activities (1.2 +/- 0.71 U/100 mg intestinal tissue, P < 0.05). Furthermore, SMA endothelial function was significantly preserved (relaxation to ACh: 57 +/- 6%, P < 0.01) in CP-0127-treated traumatic shock rats. These results indicate that bradykinin plays an important role in tissue injury associated with traumatic shock and that CP-0127 affords significant protection, which may be achieved through inhibition of neutrophil-endothelial interaction and protection of vascular endothelial function.
Volume
266
Issue
3 Pt 2
First Page
867
Last Page
873
ISSN
0002-9513
Published In/Presented At
Christopher, T. A., Ma, X. L., Gauthier, T. W., & Lefer, A. M. (1994). Beneficial actions of CP-0127, a novel bradykinin receptor antagonist, in murine traumatic shock. The American journal of physiology, 266(3 Pt 2), H867–H873. https://doi.org/10.1152/ajpheart.1994.266.3.H867
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
8160833
Department(s)
Administration and Leadership
Document Type
Article