Role of bradykinin in the actions of “New Pressor Protein” related to human plasma βFXIIa

Introduction: Experiments show that new pressor protein (NPP) and bradykinin (BK) levels increase in hypertensive anephric patients. Both NPP and BK are known to stimulate the release of adrenal medullary catecholamines so we hypothesized that NPP injections provoke the production of endogenous BK, which might contribute to the cardiac and blood pressure actions of NPP. The aim of this study was to determine the cardiac heart rate (HR) and systolic blood pressure (SBP) effects of BK in 2NX and sham-2NX (control) rats for comparison with the effects of NPP. Materials and Methods: Male Wistar rats (300-350 g) n=8 per each group were anesthetized with Inactin and ganglion blocked and prepared for bioassay. After 24 h 2NX or sham-2NX (control) Cap was given and BP and HR were recorded before/after injecting NPP (20 uL plasma equivalent i.v.) or BK at 100 or 1000 ng/kg. Results: In sham-2NX (control) rats, no Cap, NPP raised SBP by 32 ± 3 mmHg and HR by 20±3 beats/min (bpm),BK at 100 ng/kg raised SBP trivially by 2 ±1 mmHg and HR by 1 ± 0.5 bpm. BK at 1000 ng/kg, no Cap, raised SBP by 13 ±3 mmHg and HR 13 ± 2 bpm. In 2NX rats (no Cap), NPP raised SBP by 58±6 mmHg and HR by 70±14 bpm ,BK at 100 ng/kg raised the SBP by 4 ± 1 mmHg and HR by 3 ±1 bpm. With BK at 1000 ng/kg, SBP rose 6 ±1 and HR rose 2± 1 bpm. Cap injection strongly potentiated these effects in sham-2NX rats , but this treatment potentiated only BK responses in 2NX rats. Conclusion: In sham-2NX rats, the effects of BK at both lower and higher doses are the same as NPP response on SBP and HR. These effects are potentiated by Cap, but are modified differently by 2NX. Administration of HOE-140 (a specific bradykinin B2-receptor antagonist) blocked BK response completely, but this treatment blocked NPP responses moderately.Thus, BK is probably not the only mediator of NPP’s cardiovascular effects and other mechanisms need to be investigated.