Cumulative effects of AT1 and AT2 receptor blockade on ischaemia-reperfusion recovery in rat hearts.
Though ischaemia/reperfusion injury induces renin-angiotensin systemic (RAS) activation and increased heart angiotensin production, the effects of blockade of the two main angiotensin II receptors, AT1 and AT2, are not definitively established. Using a Langendorff heart preparation, effects of Valsartan 10(-7)M (AT1 receptor blocker), PD 123319 10(-7)M (AT2 receptor blocker) or both in the presence of a controlled concentration of angiotensin II (10(-8)M) in order to reproduce systemic RAS activation were studied in adult male Wistar rat hearts submitted to ischaemia/reperfusion. Ischaemia/reperfusion impaired both systolic and diastolic function through a no-reflow phenomenon. Presence of a controlled concentration of angiotensin in the perfusate, enough to produce a significant AT1-induced vasoconstriction before ischaemia, has no relevant influence on ischaemia/reperfusion injury. Only blockade of both AT1 and AT2 receptors significantly improved recovery from ischaemia; better ventricle function paralleled better perfusion. The results suggest that blockade of angiotensin II receptors is cumulative since blockade of AT1 and AT2 receptors is more effective than blockade of just one of them.
Ryckwaert
Frédérique
F
Unité INSERM U469, rue de la Cardonille, Montpellier 34094, France. f-ryckwaert@chu-montpellier.fr
Colson
Pascal
P
Guillon
Gilles
G
Foëx
Pierre
P
D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D057912:Angiotensin II Type 2 Receptor Blockers; D000818:Animals; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000502:physiology*; D044139:Receptor, Angiotensin, Type 2 / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000493:pharmacokinetics; D014633:Valine / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D000068756:Valsartan; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D000068756:Valsartan; D014633:Valine