The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill.
BACKGROUND
The renin-angiotensin and kininogen-kinin hormonal systems are critically involved in regulating blood pressure and are candidates in contributing to oral contraceptive pill (OCP)-induced hypertension. Angiotensin-converting enzyme (ACE) and aminopeptidase P (AP-P) are key enzymes in these systems and are both involved in the degradation of the vasodilator bradykinin.


METHODS
Circulating ACE and AP-P levels were measured by activity assay using selective fluorogenic peptide substrates in plasma samples from the Leeds Family Study. In addition, the effect of progesterone on the expression of AP-P and ACE was examined in cells.


RESULTS
Women on the OCP had higher age-adjusted plasma AP-P (mean [95% confidence interval]) (0.27 [0.23-0.32] nmol/min/ml (n = 53)) compared with women not on the OCP (0.17 [0.16-0.19] nmol/min/ml (n = 133), p < 0.001) or males (0.19 [0.17-0.20] nmol/min/ml (n = 209), p<0.001). There were no differences in the age-adjusted plasma ACE levels among the three groups. In HepG2 cells, progesterone treatment increased the AP-P protein and mRNA expression, whereas no effect of progesterone treatment was observed for ACE.


CONCLUSIONS
Increased AP-P may result in increased breakdown of bradykinin. These data suggest that progesterone-induced increases in AP-P may contribute to the development of OCP-induced hypertension in susceptible Women.
Cilia La Corte
Amy L
AL
Proteolysis Research Group, Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK. a.l.cilialacorte@leeds.ac.uk
Carter
Angela M
AM
Turner
Anthony J
AJ
Grant
Peter J
PJ
Hooper
Nigel M
NM
D000626:Aminopeptidases / Q000097:blood* / Q000235:genetics; D001920:Bradykinin / Q000378:metabolism*; D045744:Cell Line, Tumor; D003276:Contraceptives, Oral / Q000008:administration & dosage* / Q000494:pharmacology*; D004304:Dosage Forms; D005260:Female; D006801:Humans; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D003276:Contraceptives, Oral; D004304:Dosage Forms; D012333:RNA, Messenger; D011374:Progesterone; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin