Role of angiotensin II in the response to endothelin-1 of goat cerebral arteries after ischemia-reperfusion.
As angiotensin II may underlie the deleterious effects of some vascular diseases, we have examined the role of this peptide on the cerbrovascular endothelin-1 action after ischemia-reperfusion. In anesthetized goats, 1 hour-occlusion followed by 1 hour-reperfusion of the left middle cerebral artery (MCA) was induced, and then segments 3-mm in length from branches of the right MCA (control) and the left MCA (ischemic) were obtained for isometric tension recording. Endothelin-1 (10(-11)-10(-7) M) produced a contraction that was higher in ischemic than in control arteries, and in control but not in ischemic arteries this contraction was potentiated by angiotensin II (10(-7) M). Losartan (3 x 10(-6) M), antagonist of AT1 receptors, did not affect the response to endothelin-1 in control arteries, but reduced it both in ischemic arteries and angiotensin II-treated control arteries. PD123,319 (3 x 10(-6) M), antagonist of AT2 receptors, or the inhibitor of nitric oxide synthesis L-NAME (10(-4) M) did not alter the arterial effects of endothelin-1. Therefore, angiotensin II may potentiate the constriction to endothelin-1 in normal cerebral arteries by activating AT1 receptors. The observed cerebrovascular increased response to endothelin-1 after ischemia-reperfusion might be related in part to activation of AT1 receptors under this condition.
Salcedo
Adely
A
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, Arzobispo Morcillo, 4, 28029 Madrid, Spain.
Fernández
Nuria
N
García Villalón
Angel Luis
AL
Monge
Luis
L
Narváez Sánchez
Raúl
R
Diéguez
Godofredo
G
D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006041:Goats; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015427:Reperfusion Injury / Q000503:physiopathology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D019332:Endothelin-1; D007093:Imidazoles; D011725:Pyridines; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D011189:Potassium Chloride; D019808:Losartan