Changes in vascular distensibility during angiotensin-converting enzyme inhibition involve bradykinin type 2 receptors.
Changes in arterial stiffness and structure occur during cardiovascular diseases and can be modified by angiotensin-converting enzyme (ACE) inhibitors. In the present study we investigated the role of membrane-bound ACE (t-ACE) in the regulation of arterial structure and mechanics. Large and small arteries of t-ACE-/- mice were isolated to determine the passive pressure-diameter relationship. We observed that t-ACE-/- mice exhibit a reduced arterial distensibility compared to t-ACE+/+ mice. This reduced arterial distensibility was also observed after 9 weeks of captopril treatment (80 mg/kg/ day). We hypothesized that bradykinin type 2 receptor (BK(2)) stimulation might be involved in the regulation of arterial stiffness. t-ACE-/- and t-ACE+/+ mice were treated with Hoe 140 (1 mg/kg/day) for 14 days. After Hoe 140 treatment, both the structural and mechanical changes observed in the t-ACE-/- carotid artery were abolished. Although Hoe 140 administration increased blood pressure in both groups by approximately 10 mm Hg, the pressure difference between the two groups did not change. Thus, t-ACE is involved in the regulation of arterial distensibility. The changes observed in t-ACE-/- mice are not caused by an altered fetal development. Moreover, it is likely that the regulation of arterial distensibility by ACE involves stimulation of the BK(2) receptor.
Aartsen
Wendy M
WM
Department of Pharmacology and Toxicology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands.
Hilgers
R H P
RH
Schiffers
P M H
PM
Daemen
M J A P
MJ
De Mey
J G R
JG
Smits
J F M
JF
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology; D001158:Arteries / Q000502:physiology*; D001794:Blood Pressure; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D002339:Carotid Arteries / Q000502:physiology; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D043782:Receptor, Bradykinin B2 / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D043782:Receptor, Bradykinin B2; C065679:icatibant; D007703:Peptidyl-Dipeptidase A; D001920:Bradykinin