OBJECTIVES: There is increasing evidence that blood coagulation factors can influence blood pressure. In the present study, we tested the hypothesis that the beta fragment of human coagulation factor XIIa (beta-FXIIa) induces adrenal catecholamine-mediated pressor and chronotropic responses via bradykinin generated from the plasma kallikrein-kinin system. METHODS AND RESULTS: In anaesthetized bioassay rats with blocked autonomic reflexes, in the Brown Norway strain a bolus injection of beta-FXIIa (1 microg/kg, administered intravenously) elicited a 170-fold rise in plasma epinephrine (from 0.12 +/- 0.02 to 20.58 +/- 2.42 nmol/l; P < 0.001) and a fivefold increase in plasma norepinephrine (from 0.11 +/- 0.02 to 0.57 +/- 0.09 nmol/l; P < 0.01), concurrent increases in systolic blood pressure (from 70 +/- 5 to 101 +/- 4 mmHg; P < 0.01) and heart rate (from 315 +/- 11 to 408 +/- 15 bpm; P < 0.01), and a doubling of bradykinin concentrations (P < 0.05). Bilateral adrenal medullectomy abolished both the catecholamine and the haemodynamic responses to beta-FXIIa. Catecholamine, bradykinin and haemodynamic responses to beta-FXIIa were absent in plasma kininogen-deficient Brown Norway Katholiek (BNK) rats. Exogenous bradykinin dose-dependently reproduced these catecholamine and haemodynamic responses in Brown Norway and BNK rats, but not in Brown Norway adrenal medullectomized rats. CONCLUSION: The pressor and chronotropic responses to beta-FXIIa in this bioassay preparation are mediated exclusively through adrenal catecholamine release, and require plasma kininogens for their full expression. These observations suggest that interaction between the coagulation, kallikrein-kinin and sympatho-adrenal systems can exert important pressor effects in the absence of counterregulatory autonomic reflexes.
OBJECTIVES: There is increasing evidence that blood coagulation factors can influence blood pressure. In the present study, we tested the hypothesis that the beta fragment of human coagulation factor XIIa (beta-FXIIa) induces adrenal catecholamine-mediated pressor and chronotropic responses via bradykinin generated from the plasma kallikrein-kinin system. METHODS AND RESULTS: In anaesthetized bioassay rats with blocked autonomic reflexes, in the Brown Norway strain a bolus injection of beta-FXIIa (1 microg/kg, administered intravenously) elicited a 170-fold rise in plasma epinephrine (from 0.12 +/- 0.02 to 20.58 +/- 2.42 nmol/l; P < 0.001) and a fivefold increase in plasma norepinephrine (from 0.11 +/- 0.02 to 0.57 +/- 0.09 nmol/l; P < 0.01), concurrent increases in systolic blood pressure (from 70 +/- 5 to 101 +/- 4 mmHg; P < 0.01) and heart rate (from 315 +/- 11 to 408 +/- 15 bpm; P < 0.01), and a doubling of bradykinin concentrations (P < 0.05). Bilateral adrenal medullectomy abolished both the catecholamine and the haemodynamic responses to beta-FXIIa. Catecholamine, bradykinin and haemodynamic responses to beta-FXIIa were absent in plasma kininogen-deficient Brown Norway Katholiek (BNK) rats. Exogenous bradykinin dose-dependently reproduced these catecholamine and haemodynamic responses in Brown Norway and BNK rats, but not in Brown Norway adrenal medullectomized rats. CONCLUSION: The pressor and chronotropic responses to beta-FXIIa in this bioassay preparation are mediated exclusively through adrenal catecholamine release, and require plasma kininogens for their full expression. These observations suggest that interaction between the coagulation, kallikrein-kinin and sympatho-adrenal systems can exert important pressor effects in the absence of counterregulatory autonomic reflexes.