HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 286/3/H837    most recent 00693.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Papageorgiou, P. C. Articles by Osmond, D. H. Search for Related Content PubMed PubMed Citation Articles by Papageorgiou, P. C. Articles by Osmond, D. H.

Are cardiovascular and sympathoadrenal effects of human "new pressor protein" preparations attributable to human coagulation -FXIIa?

¹Departments of Physiology and Medicine, University of Toronto, Toronto, Ontario M5S1A8; ²Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario M5S3E2; ³Institute of Medical Science, University of Toronto, Toronto, Ontario M5S1A8; ⁴Department of Laboratory Medicine and Pathobiology, University of Toronto and Mount Sinai Hospital, Toronto, Ontario, Canada M5G1X5; ⁵Department of Internal Medicine, Erasmus Medical Centre, Rotterdam 3015 GD, The Netherlands

Submitted 18 July 2003 ; accepted in final form 20 October 2003

"New pressor protein" (NPP) derived from normal human plasma is an extra renal enzyme that shares strong sequence homology with human coagulation -FXIIa. Under our bioassay conditions, human NPP (10–20 µl plasma equivalent/300 g rat iv) can raise the systolic blood pressure (SBP) by 40–50 mmHg, the diastolic blood pressure (DBP) by 15–20 mmHg, and the heart rate (HR) by 70–90 beats/min. Plasma epinephrine (of adrenal medullary origin) and norepinephrine rise by about 50- and 10-fold, respectively. Because -FXIIa is not normally associated with pressor properties, we endeavored to substantiate that the hypertensive effects of impure NPP preparations used in our experiments are attributable to their content of -FXIIa. We carried out comparisons with highly purified (>90%) commercial human -FXIIa and found that by gel filtration (Sephadex G-100 and G-75), NPP bioactivity appeared in the 30-kDa elution zone, consistent with the molecular mass of -FXIIa. Retention time using fast-protein liquid chromatography anion exchange chromatography was identical. Molecular mass and comigration were confirmed by SDS-PAGE gel electrophoresis, and the recovered 30-kDa protein bands yielded -FXIIa fragments identified by mass spectrometry. Matched doses of the NPP preparations produced dose-response curves very similar to those elicited by -FXIIa with respect to increments of SBP, DBP, and HR, whereas plasma catecholamine increments were generally comparable. We propose that -FXIIa is substantially, if not exclusively, responsible for the observed effects of our NPP preparations and that this points to a novel axis connecting the FXII coagulation cascade and the sympathoadrenal gland to other cardiovascular regulatory mechanisms.

Hageman fragment factor; hypertension; catecholamines