Potent blood pressure raising effects of activated coagulation factor XII.

A new pressor protein (NPP) in trypsin-activated human plasma was recently reported, whose blood pressure raising effects in bioassay rats are potentiated 300% after treatment with angiotensin I converting enzyme inhibitors (captopril). Pure NPP showed good N-terminal sequence homology with coagulation factor beta FXIIa, and little of it was present in FXII-deficiency plasmas (> or = 99%, n = 4). The present experiments confirm this in four additional FXII-deficiency plasmas. Further, (i) adding highly purified coagulation FXII, alpha FXIIa, or beta FXIIa fragment restores pressor activity to such plasmas, but only after activation with trypsin. (ii) Such requirement for trypsin suggests that no factor is structurally identical with NPP to begin with but that all can be activated to NPP. (iii) When injected directly by vein, only beta FXIIa is pressor, suggesting closest structural resemblance to NPP and (or) readiest endogenous conversion to NPP. (iv) NPP and beta FXIIa are cardiotonic: they both raise systolic pressure more than the diastolic, with a concomitant increase in heart rate. These observations support NPP's structural relationship with beta FXIIa and connect coagulation and blood pressure mechanisms in a new way, whose significance to the physiology and pathophysiology of blood pressure regulation remains to be established.