Beneficial effects of combined blockade of ACE and AT1 receptor on intimal hyperplasia in balloon-injured rat artery.
OBJECTIVE
The present study was undertaken to elucidate the effect of the ACE inhibitor and the angiotensin II type 1 (AT1) receptor antagonist in combination on neointimal hyperplasia after balloon injury.


RESULTS
Temocapril (an ACE inhibitor), CS-866 (an AT1 receptor antagonist), or their combination was given orally to rats, and their effects were compared on vascular hyperplasia induced by balloon injury. The maximal preventive effect of temocapril and CS-866 alone on neointimal thickening after balloon injury was obtained at a dose of 20 and 10 mg/kg per day, respectively. However, compared with either agent alone, combined temocapril and CS-866 (20 and 10 mg/kg per day, respectively) prevented intimal thickening to a larger extent. Furthermore, compared with either agent alone, combined temocapril and CS-866 prevented vascular smooth muscle cell proliferation in the intima more potently. The increase in platelet-derived growth factor receptor tyrosyl phosphorylation was reduced more potently by the combination of both agents compared with either agent alone. The nonpeptide bradykinin B2 receptor antagonist or the NO synthase inhibitor reduced the prevention of intimal thickening by combined temocapril and CS-866.


CONCLUSIONS
Compared with either agent alone, the combination of an ACE inhibitor and an AT1 receptor antagonist is more effective in the prevention of vascular hyperplasia due to bradykinin or NO.
Kim
Shokei
S
Department of Pharmacology, Osaka City University Medical School, Osaka, Japan. kims@med.osaka-cu.ac.jp
Izumi
Yasukatsu
Y
Izumiya
Yasuhiro
Y
Zhan
Yumei
Y
Taniguchi
Masaru
M
Iwao
Hiroshi
H
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D002455:Cell Division; D003404:Creatinine / Q000097:blood; D006965:Hyperplasia / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000068557:Olmesartan Medoxomil; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D013841:Thiazepines / Q000494:pharmacology; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*; D014443:Tyrosine / Q000378:metabolism
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; C106745:FR 167344; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D013841:Thiazepines; D014443:Tyrosine; D000068557:Olmesartan Medoxomil; C055603:temocapril hydrochloride; D003404:Creatinine; D020797:Receptor, Platelet-Derived Growth Factor beta; D019331:NG-Nitroarginine Methyl Ester