Characterisation of angiotensin converting enzyme from different rat vascular beds.
The tissue renin angiotensin system may play a role in cardiovascular pathophysiology. Angiotensin converting enzyme in tissues is now a target for pharmacological inhibition. It is therefore important to determine whether ACE is evenly distributed throughout the vascular tree and whether the enzyme has the same characteristics in different vascular beds. We have thus measured angiotensin converting enzyme density in three functionally different vascular beds with three different methods: the enzyme kinetic assay, a radioligand binding assay and in vitro autoradiography. All three methods demonstrated a significantly higher binding density and activity of ACE in resistance arteries from the mesenteric vascular bed of rats than in microvessels from the brain, or in a conduit artery, the aorta. The dissociation constant (Kd) of the enzyme-radioligand complex was the same in the three functionally different vessel types. Radioligand displacement studies for ACE from plasma and the mesenteric vessels in vitro utilizing a panel of different ACE inhibitors have shown a similar rank order of inhibitory potency suggesting that catalytic sites of ACE were the same in plasma and the mesenteric microvessels. In vivo, the enzyme inhibition in plasma, mesenteric and brain vessels measured by enzyme kinetic and radioligand binding assay were well correlated. There was a similar degree of inhibition between different vessels and tissues (mesenteric vessels, aorta, kidney, left ventricle and coronaries) measured by in vitro autoradiography.
Jandeleit-Dahm
K
K
University of Melbourne, Department of Medicine, Austin & Repatriation Hospitals, Heidelberg, Victoria, Australia.
Jackson
B
B
Paxton
D
D
Perich
R
R
Johnston
C I
CI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000201:enzymology*; D001665:Binding Sites; D001921:Brain / Q000098:blood supply*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002384:Catalysis; D008297:Male; D008638:Mesenteric Arteries / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000032:analysis*; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; C065499:zabicipril; D007703:Peptidyl-Dipeptidase A