The Effects of Human New Pressor Protein and Coagulation Factor XIIa on Blood Pressure and Heart Rate in Bilaterally Nephrectomized Rats

Background: New Pressor Protein (NPP) is a human plasma enzyme structurally related to b–fragment of activated factor XІІ (β-FXIIa). The objective of the present study was to investigate the effects of NPP and β-FXIIa on systolic blood pressure and heart rate in bilateral nephrectomized rats. Methods: Forty male Wistar rats (250-300 g) were sham-operated or bilaterally nephrectomized under anesthesia with a combination of halothane, nitrous oxide and oxygen. Twenty four hours later under anesthesia with Inactin (100 mg/kg), they were ganglion blocked (pentolinium tartrate; 19.2 mg/kg), and their systolic blood pressure and heart rate were measured before and after intravenous administration of captopril (2.5 mg/kg), NPP (20μl plasma equivalent) or purified β-FXIIa (300 ng/kg). Results: NPP raised the systolic blood pressure by 31±2 mmHg and heart rate by 19±2 bpm in sham-operated rats. Captopril caused systolic blood pressure and heart rate to increase significantly by 64±7 mmHg and 107±9 bpm, respectively in response to NPP. In bilateral nephrectomized rats, NPP raised systolic blood pressure by 57±6 mmHg and heart rate by 70±13 bpm in the absence of captopril, which were not significantly different from those (46±3 mmHg and 75±8 beats/min) in the presence of captopril. Conclusion: This study shows that the effects of NPP and β-fragment of factor XІІ on systolic blood pressure and heart rate are similar, suggestive of a functional relationship between them. The findings might suggest that the potentiation effect of captopril in sham-operated or bilaterally nephrectomized rats is primarily expressed via renal enzymes.