Captopril and the intestinal response to hemorrhagic shock.
In order to help clarify the role of the renin-angiotensin system in the evolution of the post-hemorrhagic circulatory shock syndrome, captopril, a potent inhibitor of the conversion of angiotensin I to angiotensin II, was infused into a hemorrhagic shock model in the cat. The hemorrhage protocol had arterial blood withdrawn until a mean arterial blood pressure (MABP) of 40 mm Hg developed. Oligemia was maintained for a period of 2.5 hr, after which time, all remaining shed blood was reinfused and the cats observed for an additional 2 hr. Coincident with the large reduction in MABP, superior mesenteric artery flow (SMAF) was similarly reduced as recorded by a noncannulating electromagnetic flow probe fitted around the artery. Post-oligemic plasma activities of cathepsin D (CD) and alkaline phosphatase (AP) were elevated 11-fold and 3-fold respectively; intestinal morphological damage was graded at 2.8 +/- 0.6 on a 0-4 scale of increasing severity (control: 0.03 +/- 0.02). Captopril was administered at an initial priming dose of 0.5 mg/kg followed by a continuous infusion of 0.5 mg/kg/hr. Improved post-reinfusion maintenance of MABP and SMAF was noted. Plasma elevations in enzyme activity were more moderate: 8-fold for CD, 1.5-fold for AP. Intestinal morphologic damage was graded at 2.5 +/- 0.3. Blockade of angiotensin II formation by captopril thus demonstrated beneficial effects on post-oligemic hemodynamic status and on the degree of cellular enzyme release without significant improvement in intestinal morphology.
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D002402:Cathepsin D; D002403:Cathepsins / Q000494:pharmacology; D002415:Cats; D006439:Hemodynamics / Q000187:drug effects; D007422:Intestines / Q000098:blood supply*; D008297:Male; D011392:Proline / Q000031:analogs & derivatives*; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000187:drug effects
D011392:Proline; D002216:Captopril; D000469:Alkaline Phosphatase; D002403:Cathepsins; D002402:Cathepsin D