The bradykinin-degrading aminopeptidase P is increased in women taking the oral contraceptive pill

Abstract

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. 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. 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. 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.