Role of bradykinin and eNOS in the anti-ischaemic effect of trandolapril

British Journal of Pharmacology
A CargnoniR Ferrari

Abstract

1. Angiotensin converting enzyme (ACE) inhibitors are under study in ischaemic heart diseases, their mechanism of action being still unknown. 2. The anti-ischaemic effect of trandolapril and the possible involvement of a bradykinin-modulation on endothelial constitutive nitric oxide synthase (eNOS) in exerting this effect, were investigated. 3. Three doses of trandolapril, chronically administered in vivo, were studied in isolated perfused rat hearts subjected to global ischaemia followed by reperfusion. 4. Trandolapril has an anti-ischaemic effect. The dose of 0.3 mg kg(-1) exerted the best effect reducing diastolic pressure increase during ischaemia (from 33.0+/-4.5 to 14.0+/-5.2 mmHg; P<0.05 vs control) and reperfusion (from 86.1+/-9.4 to 22.2+/-4.1 mmHg; P<0.01 vs control), improving functional recovery, counteracting creatine phosphokinase release and ameliorating energy metabolism after reperfusion. 5. Trandolapril down-regulated the baseline developed pressure. 6. Trandolapril increased myocardial bradykinin content (from 31.8+/-6.1 to 54.8+/-7.5 fmol/gww; P<0.05, at baseline) and eNOS expression and activity in aortic endothelium (both P<0.01 vs control) and in cardiac myocytes (from 11.3+/-1.5 to 17.0+/-2.0 mUOD microg...Continue Reading

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Citations

Dec 27, 2011·Cellular and Molecular Neurobiology·Kirtiman SrivastavaUlvi Bayraktutan
Jun 14, 2005·Pharmacology & Therapeutics·R SchulzJ-L Balligand
Jul 10, 2002·Journal of the American College of Cardiology·Antti KuoppalaKen A Lindstedt
Aug 27, 2003·Southern Medical Journal·John P Higgins
Apr 27, 2004·Proceedings of the National Academy of Sciences of the United States of America·Brian G DrewBronwyn A Kingwell
Apr 4, 2014·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Atsuko NonakaMasafumi Kitakaze
Aug 13, 2013·Postgraduate Medicine·James J DinicolantonioJames H O'Keefe
Mar 5, 2013·International Journal of Cardiology·R Ferrari, G M Rosano

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