Differential effects of imidapril and candesartan cilexetil on plasminogen activator inhibitor-1 expression induced by prolonged inhibition of nitric oxide synthesis in rat hearts.
We investigated effects of the angiotensin-converting enzyme (ACE) inhibitor imidapril and the angiotensin II type 1 (AT1) antagonist candesartan cilexetil on cardiac plasminogen activator inhibitor-1 (PAI-1) expression in rats. Cardiac PAI-1 mRNA levels were increased after a 7-day treatment with the nitric oxide (NO) synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). PAI-1 immunoreactivity was increased in the coronary arteries. Treatment with imidapril significantly prevented the L-NAME-induced increase in the gene expression and immunoreactivity of PAI-1, but candesartan cilexetil showed no such effect. This study provides the first evidence of differential effects of ACE inhibition and AT1 antagonism on cardiac PAI-1 expression in vivo.
Katoh
M
M
Discovery Research Laboratory, Tanabe Seiyaku Co., Ltd., Toda, Saitama, Japan. katoh-m@tanabe.co.jp
Egashira
K
K
Mitsui
T
T
Takeshita
A
A
Narita
H
H
D000199:Actins / Q000235:genetics; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly; D003094:Collagen / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007150:Immunohistochemistry; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles
D000199:Actins; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D048289:Imidazolidines; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D009569:Nitric Oxide; D003094:Collagen; C065166:imidapril; C077793:candesartan cilexetil; D019331:NG-Nitroarginine Methyl Ester