Adrenomedullary catecholamine, pressor and chronotropic responses to human coagulation beta-FXIIa mediated by endogenous kinins.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Amfilochiadis
Akis A
AA
University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, Canada.
Backx
Peter H
PH
Floras
John S
JS
D000313:Adrenal Medulla / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000097:blood / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D015956:Factor XIIa / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007704:Kininogens / Q000097:blood / Q000172:deficiency; D008297:Male; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011914:Rats, Inbred BN; D011922:Rats, Mutant Strains; D017208:Rats, Wistar; D013997:Time Factors
D002395:Catecholamines; D007704:Kininogens; D010446:Peptide Fragments; D015956:Factor XIIa; D001920:Bradykinin; D009638:Norepinephrine; D004837:Epinephrine