Angiotensin II activates NADPH oxidase in isolated rat hearts subjected to ischaemia-reperfusion.
The role of angiotensin II in myocardial ischaemia-reperfusion is not clearly defined. In this respect, the involvement of NADPH oxidase remains to be determined. The aim of this study was 1) to evaluate the cardiac effects of angiotensin AT(1) receptor stimulation in non-ischaemic conditions of perfusion or during ischaemia-reperfusion, and 2) to measure the concomitant activation of NADPH oxidase in isolated rat hearts perfused with angiotensin II and/or Losartan. In non-ischaemic hearts, angiotensin II induced rapid and prolonged vasoconstrictive and negative inotropic effects. Ischaemia-reperfusion increased the mRNA expression of AT(1) and AT(2) receptors. During reperfusion, angiotensin II reduced the incidence of arrhythmias and the lactate dehydrogenase released, and increased NADPH oxidase mRNA expression and enzyme activity. Losartan co-administration totally antagonised the effects of angiotensin II. Our study demonstrates that ischaemia-reperfusion induces adaptative cardiac modifications, which allow exogenously added angiotensin II to stimulate myocardial NADPH oxidase through angiotensin AT(1) receptor activation.
Oudot
Alexandra
A
Laboratoire de Physiopathologie et Pharmacologie Cardio-vasculaires Expérimentales, Faculties of Medicine and Pharmacy, 7, Boulevard Jeanne d'Arc, BP 87900, 21079 Dijon, France. aoudot@hotmail.com
Vergely
Catherine
C
Ecarnot-Laubriet
Aline
A
Rochette
Luc
L
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D003326:Coronary Circulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins; D017202:Myocardial Ischemia / Q000150:complications*; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010477:Perfusion; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D007770:L-Lactate Dehydrogenase; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; C086986:CYBA protein, human; D009252:NADPH Dehydrogenase; D019808:Losartan