The sympathoadrenal system mediates the blood pressure and cardiac effects of human coagulation factor XII-related "new pressor protein".
OBJECTIVE
To investigate the major cardiovascular effects of human plasma "new pressor protein" (NPP) and how the adrenal medulla contributes to these effects.


METHODS
NPP was injected into bioassay rats intravenously, and the effects on blood pressure and cardiac function were investigated. Acute adrenal medullectomy (2MDX), alpha- and beta-adrenergic blockade and plasma catecholamine levels were also used to evaluate the role of the sympathoadrenal system in mediating the NPP effects.


RESULTS
NPP significantly raised systolic blood pressure (SBP) and mean arterial pressure but not diastolic blood pressure (DBP), with no significant change in total peripheral resistance. Heart rate, cardiac output and stroke volume rose by 16%, 53% and 36%, respectively. Plasma catecholamines increased massively, notably adrenaline, raising the adrenaline to noradrenaline ratio from about 4:1 to 18:1. 2MDX attenuated the increments of SBP and heart rate by more than 90% and more than 70%, respectively, implicating the adrenal medulla. Beta-adrenergic blockade (propranolol) potentiated the NPP-induced increase of SBP and DBP, but not that of heart rate. Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol) blocked the rise in SBP, DBP and heart rate.


CONCLUSIONS
NPP's hypertensive action is attributable mainly to increases in systolic blood pressure, heart rate and cardiac output (an increase in heart rate and stroke volume) with massive release of adrenal medullary catecholamines. Such effects suggest a novel axis between coagulation factor XII and the sympathoadrenal system, the cardiovascular effects of which are controlled by combined alpha- and beta-adrenergic blockade, but not by angiotensin-converting enzyme inhibition. Clinical relevance depends on whether NPP is formed in vivo in thrombotic states.
Mavrogiannis
Louie
L
Departments of Physiology and Medicine, Faculty of Medicine, University of Toronto, Medical Sciences Building, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.
Trambakoulos
Dimitra M
DM
Boomsma
Frans
F
Osmond
Daniel H
DH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001795:Blood Pressure Determination; D001798:Blood Proteins / Q000494:pharmacology / Q000502:physiology*; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D005174:Factor XII / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D006334:Heart Function Tests; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012680:Sensitivity and Specificity; D014361:Trypsin Inhibitors / Q000494:pharmacology / Q000502:physiology; D014655:Vascular Resistance
D000806:Angiotensin-Converting Enzyme Inhibitors; D001798:Blood Proteins; D002395:Catecholamines; D014361:Trypsin Inhibitors; D005174:Factor XII; D011433:Propranolol