Alteration of local ACE activity and vascular responsiveness during development of 2K1C renovascular hypertension.
OBJECTIVE
This study sought to examine the correlation between development of hypertension and local, including; aorta, heart, kidney, lung, as well as circulatory (serum) ACE activity in two kidney one clip (2K1C) renovascular hypertension.


METHODS
Ten- to twelve-week-old rats undertaken left renal artery clipping. Experiments were carried out in 2, 4, 8, and 12 weeks after induction of hypertension (2, 4, 8 and 12W). After sacrificing, animals blood and tissues including heart, aorta lung and kidney were dissected out and homogenized in Trizma buffer. ACE activity was determined by hydrolysis of the synthetic substrate, Hip-His-Leu and the amount of hippuric acid liberated from the substrate were analyzed by HPLC. Vascular responsiveness was measured using perfusion pressure method.


RESULTS
The systolic blood pressure (SBP) was gradually increased in 2K1C animals and was markedly higher compared to that of controls. The ACE activity in all tissues from 2K1C was significantly different in all groups of 2, 4, 8, and 12 weeks after surgery. The serum ACE activity of 2K1C was markedly increased in 2 and 4W and reached to plateau in 8 and 12W group. Vascular responsiveness to angiotensin I (AngI) was increased during development of hypertension in all groups of animals.


CONCLUSIONS
These results indicated that there is a positive correlation between augmentation of blood pressure and local ACE activity in various tissues as well as serum, highlighting the significant contribution of local compared to circulatory ACE activity in development of renovascular hypertension.
Sharifi
Ali M
AM
Department of Pharmacology and Cellular & Molecular Research Center, School of Medicine, Iran University of Medical Sciences, P.O. Box 14155-6183, Tehran, Iran. sharifal@yahoo.com
Akbarloo
Nasrin
N
Heshmatian
Behnam
B
Ziai
Ali
A
D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006978:Hypertension, Renovascular / Q000201:enzymology* / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A