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

J Renin Angiotensin Aldosterone Syst. 2008 Dec;9(4):221-5. doi: 10.1177/1470320308096405.

Abstract

Introduction: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / blood*
  • Aminopeptidases / genetics
  • Bradykinin / metabolism*
  • Cell Line, Tumor
  • Contraceptives, Oral / administration & dosage*
  • Contraceptives, Oral / pharmacology*
  • Dosage Forms
  • Female
  • Humans
  • Male
  • Peptidyl-Dipeptidase A / blood
  • Progesterone / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Contraceptives, Oral
  • Dosage Forms
  • RNA, Messenger
  • Progesterone
  • Aminopeptidases
  • X-Pro aminopeptidase
  • Peptidyl-Dipeptidase A
  • Bradykinin