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Enzymic “New Pressor protein" (NPP) from activated human plasma, with homology to β fragment of XII coagulation factor (βFXIIa ), potently raises blood pressure and heart rate when given i.v. to bioassay animals. Concurrently, there is a massive rise of plasma catecholamines, which must be primarily of adrenal medullary origin because all these effects are largely abolished by acute adrenal medullectomy. We postulate that peptides resulting from i.v. injection of NPP act as mediators of its action on the sympatho- adrenal , establishing an axis that connects XII coagulation factor, derivative peptides, and the sympatho-adrenal system to produce these cardiovascular effects. Endogenous NPP may not circulate in healthy animals or humans but could be produced from endogenous XII coagulation factor should it be activated in pathophysiological states involving endothelial dysfunction, inflammation or thrombosis. Such endogenous NPP could conceivably cause clinical effects similar to those reported here in a manner that counteracts the normally very beneficial therapeutic effects of Angiotensin Converting Enzyme inhibition.

Keywords: NPP; XII coagulation factor; Captopril; Renin- Angiotensin System

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