title: Angiotensin II type 1 receptor blocker preserves tolerance to ischemia-reperfusion injury in Dahl salt-sensitive rat heart.
abstract: Oxidative stress is involved in the tolerance to ischemia-reperfusion (I/R) injury. Because angiotensin II type 1 receptor blockers (ARBs) inhibit oxidative stress, there is concern that ARBs abolish the tolerance to I/R injury. Dahl salt-sensitive (DS) hypertensive and salt-resistant (DR) normotensive rats received an antioxidant, 2-mercaptopropionylglycine (MPG), or an ARB, losartan, for 7 days. Losartan and MPG significantly inhibited oxidative stress as determined by tissue malondialdehyde + 4-hydroxynoneal and increased expression of inducible nitric oxide synthase (iNOS) in the DS rat heart. However, losartan but not MPG activated endothelial nitric oxide synthase (eNOS) as assessed by phosphorylation of eNOS on Ser1177. Infarct size after 30-min left coronary artery occlusion followed by 2-h reperfusion was comparable between DS and DR rat hearts. Although MPG and losartan had no effect on infarct size in the DR rat heart, MPG but not losartan significantly increased infarct size in the DS rat heart. A selective iNOS inhibitor, 1400W, increased infarct size in the DS rat heart, but it had no effect on infarct size in the losartan-treated DS rat heart. However, a nonselective NOS inhibitor, Nomega-nitro-l-arginine methyl ester, increased infarct size in the losartan-treated DS rat heart. These results suggest that losartan preserves the tolerance to I/R injury by activating eNOS despite elimination of redox-sensitive upregulation of iNOS and iNOS-dependent cardioprotection in the DS rat heart.
authors.affiliation: Second Department of Internal Medicine, Kansai Medical University, Moriguchi City, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Matsuhisa
authors.forename: Hajime
authors.initials: H
authors.lastname: Otani
authors.forename: Toru
authors.initials: T
authors.lastname: Okazaki
authors.forename: Koji
authors.initials: K
authors.lastname: Yamashita
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Akita
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sato
authors.forename: Akira
authors.initials: A
authors.lastname: Moriguchi
authors.forename: Hiroji
authors.initials: H
authors.lastname: Imamura
authors.forename: Toshiji
authors.initials: T
authors.lastname: Iwasaka
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000578:Amidines / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology; D004195:Disease Models, Animal; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051381:Rats; D020303:Rats, Inbred Dahl; D017673:Sodium Chloride, Dietary; D008625:Tiopronin / Q000494:pharmacology*; D015854:Up-Regulation; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000447:Aldehydes; D000578:Amidines; D047228:Angiotensin II Type 1 Receptor Blockers; D000975:Antioxidants; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D017673:Sodium Chloride, Dietary; D008315:Malondialdehyde; D008625:Tiopronin; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D019808:Losartan; C027576:4-hydroxy-2-nonenal; D019331:NG-Nitroarginine Methyl Ester