Role of bradykinin B2-receptor in the sympathoadrenal effects of 'new pressor protein' related to human blood coagulation factor XII fragment

Background: Human plasma new pressor protein (NPP) increases blood pressure, heart rate and plasma adrenal medullary catecholamines in bioassay rats - all potentiated by angiotensin-converting enzyme (ACE) inhibition. High plasma NPP activity has been found in haemodialysis patients with hypertension. Objective: To investigate whether the bradykinin B2-receptor mediates the effects of NPP. Methods and results: Male Wistar bioassay rats were anaesthetized with inactin, ganglion blocked with pentolinium and injected intravenously (i.v.) with human NPP (20 μl plasma equivalent) or bradykinin (100 ng/kg). Both NPP and bradykinin increased systolic (SBP) and diastolic (DBP) blood pressures, heart rate and plasma adrenaline and noradrenaline concentrations. All these responses were potentiated by the ACE inhibitor, captopril (10 mg/kg i.v.), but not by antagonism of the angiotensin II type 1 receptor with losartan (10 mg/kg i.v.). Administration of the bradykinin B2-receptor antagonist, HOE-140 (20 μg/kg i.v.), significantly attenuated the peak NPP responses as follows: SBP from 58 ± 3 to 40 ± 4 mmHg (decrease of 30%; P < 0.05); DBP from 22 ± 4 to 10 ± 1 mmHg (decrease of 55%; P < 0.05); heart rate from 124 ± 8 to 28 ± 6 beats/min (decrease of 77%; P < 0.05); plasma adrenaline from 14297 ± 2477 to 3318 ± 1105 pg/ml (decrease of 77%; P < 0.05) and noradrenaline from 505 ± 66 to 77 ± 29 pg/ml (decrease of 85%; P < 0.05). Conclusions: The haemodynamic and sympathoadrenal effects of NPP involve substantial mediation by the bradykinin B2-receptor, in addition to other mechanisms.

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