Bradykinin metabolism and hypotensive transfusion reactions

The Development of a Novel Molecular Assay Examining the Role of Aminopeptidase P Polymorphisms in Acute Hypotensive Transfusion Reactions

“…A patient with a classic acute hypotensive transfusion reaction was defined as having an acute drop in blood pressure upon transfusion without other associated signs and symptoms. 2,3 The hypotension must then have resolved upon cessation of the transfusion. Pretransfusion whole blood samples from transfusion recipients were collected into Vacutainer tubes (BD Diagnostics, Franklin Lakes, New Jersey) containing the anticoagulant EDTA.…”

“…More importantly, APP is the enzyme primarily responsible for the degradation of desArg 9 -bradykinin, the active metabolite of bradykinin. 3,[13][14][15] Notably, the XPNPEP2 gene responsible for coding membrane-bound APP is polymorphic.…”

“…3 Some studies have also shown that bradykinin accumulation and hypotensive episodes may be exacerbated in transfused patients taking angiotensin-converting enzyme (ACE) inhibitors (ACE-Is), because ACE is a key enzyme in the degradation of bradykinin. [3][4][5][6][7][8][9][10][11] However, based on reports of acute hypotensive transfusion reactions occurring in the absence of ACE-I use, 5,12 it is possible that other pathways may contribute to the accumulation of bradykinin and/or their metabolites and result in hypotension in the setting of transfusion.…”

“…More importantly, APP is the enzyme primarily responsible for the degradation of desArg 9 -bradykinin, the active metabolite of bradykinin. 3,[13][14][15] Notably, the XPNPEP2 gene responsible for coding membrane-bound APP is polymorphic. 14,15 The C-2399A single-nucleotide polymorphism (SNP) in XPNPEP2 results in a substantially truncated APP protein that cannot adequately bind to the membrane of host epithelial cells, thereby reducing its ability to participate in bradykinin/bradykinin metabolite degradation.…”

Effects of Bradykinin on Cardiovascular Remodeling in Renovascular Hypertensive Rats

“…This beneficial action is presumed to occur through the production of nitric oxide (NO) and/or prostacyclines (7,8). In recent years, studies in a mouse with targeted disruption of the BK B2 receptor gene have provided important insights into the role of BK in the cardiovascular system.…”