title: Effects of hormone replacement therapy on serum angiotensin-converting enzyme activity and plasma bradykinin in postmenopausal women according to angiotensin-converting enzyme-genotype.
abstract: An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene determines serum ACE levels. The D allele is associated with increased ACE activity and is linked to cardiovascular disease. Hormone replacement therapy (HRT) in postmenopausal women (PMW) decreases serum ACE activity and concomitantly increases plasma bradykinin. We investigated the effect of HRT on these parameters in PMW according to ACE-genotype. We assessed 68 PMW during 12-month oral HRT (0.625 mg conjugated estrogen +2.5 mg medroxyprogesterone acetate). ACE genotype was determined at baseline, and serum ACE activity and plasma bradykinin were measured at baseline and after 3-, 6-, and 12-month HRT. We divided the PMW into three groups according to ACE genotype: groups I/I (n = 26), I/D (n = 33), and D/D (n = 9). HRT resulted in a significant reduction in the genotype-associated increase in ACE activity in the ACE I/D and D/D groups after 6-month (p < 0.001 and p < 0.05, respectively) and 12-month HRT (p < 0.001 and p < 0.01, respectively), but not in the I/I group. While the reduction of ACE activity was expected to increase bradykinin in the ACE I/D and D/D groups, HRT significantly increased the bradykinin levels not only in these two groups but also in the ACE I/I group at both 6 months (p < 0.01, p < 0.05, and p < 0.001, respectively) and 12 months after the start of HRT (p < 0.01, p < 0.01, and p < 0.01, respectively). These results suggest that the increased plasma bradykinin of PMW by HRT might not be induced solely by the reduction in serum ACE activity.
authors.affiliation: Second Department of Internal Medicine, Gunma University School of Medicine, Showa-machi, Maebashi, Japan. suminoh@med.gunma-u.ac.jp
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sumino
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Ohyama
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tsugiyasu
authors.initials: T
authors.lastname: Kanda
authors.forename: Hironosuke
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Sakamaki
authors.forename: Hideki
authors.initials: H
authors.lastname: Mizunuma
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kurabayashi
mesh_terms: D000368:Aged; D001920:Bradykinin / Q000097:blood*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000008:administration & dosage / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005838:Genotype; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D017698:Postmenopause; D045167:Progesterone Congeners / Q000008:administration & dosage
chemical_list: D004967:Estrogens; D045167:Progesterone Congeners; D005640:Follicle Stimulating Hormone; D017258:Medroxyprogesterone Acetate; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin