title: Glyceryl trinitrate-induced angiotensin-converting enzyme (ACE) inhibition in healthy volunteers is dependent on ACE genotype.
abstract: Evidence concerning the importance of angiotensin-converting enzyme (ACE) genotype in cardiovascular diseases is accumulating. The aim of this study was to investigate if nitric oxide (NO), generated from glyceryl trinitrate (GTN), affects human serum ACE activity in vivo, and if so, whether this effect was dependent on ACE genotype and (or) reflected in blood pressure reduction. A tablet containing 5 mg GTN was bucally administered for 5 minutes to 17 healthy volunteers. Blood pressure (BP) was recorded, and serum ACE activity, ACE genotype, and plasma cGMP was analyzed. GTN administration significantly reduced BP only in individuals with the deletion/deletion (DD) genotype. Sixty minutes after GTN administration, serum ACE activity was reduced in individuals with the insertion/insertion (II) and insertion/deletion (ID) genotypes, but not the DD genotype. Comparing the change in ACE activity over time between the genotypes resulted in the following: II vs. DD, p < 0.01; II vs. ID, p < 0.05; and ID vs. DD, p < 0.05. There was no significant difference in plasma cGMP content neither between the ACE genotypes nor before and after GTN administration. In conclusion, GTN inhibits serum ACE in vivo in individuals with the II and ID, but not the DD genotype.
authors.affiliation: Division of Pharmacology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, SE-58185 Linköping, Sweden. Karin.Persson@imv.liu.se
authors.forename: Karin
authors.initials: K
authors.lastname: Persson
authors.forename: Annette C E
authors.initials: AC
authors.lastname: Säfholm
authors.forename: Rolf G G
authors.initials: RG
authors.lastname: Andersson
authors.forename: Johan
authors.initials: J
authors.lastname: Ahlner
mesh_terms: D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D007703:Peptidyl-Dipeptidase A; D005996:Nitroglycerin; D006152:Cyclic GMP