Role of α-adrenoceptors and prostacyclin in the enhanced adrenergic reactivity of goat cerebral arteries after ischemia-reperfusion

To analyze ischemia-reperfusion effects on the cerebrovascular adrenergic response, the left middle cerebral artery (MCA) of anesthetized goats was occluded for 120 min and reperfused for 60 min. Isolated segments from the left (ischemic) and right (control) MCA exhibited isometric constriction in response to noradrenaline (10− 8–10− 4 M, in the presence of β-adrenoceptors blockade), phenylephrine (α1-adrenoceptors agonist, 10− 8–10− 4 M), B-HT-920 (α2-adrenoceptors agonist, 10− 7–3 × 10− 3 M) or tyramine (indirect sympatheticomimetic amine, 10− 8–10− 4 M), but this constriction was greater in ischemic arteries. The cyclooxygenase (COX) inhibitor meclofenamate (10− 5 M) augmented the response to noradrenaline only in control arteries. The prostacyclin (PGI2) synthesis inhibitor tranylcypromine (TCP, 10− 5 M) increased the response to noradrenaline in control arteries and reduced it in ischemic arteries. The thromboxane A2 (TXA2) synthase inhibitor furegrelate (10− 6 M) did not modify the noradrenaline effect in both types of arteries, whereas the TXA2 receptor antagonist SQ 29 548 (10− 5 M) and the COX-2 inhibitor NS-398 (10− 6 M) decreased the response to noradrenaline only in ischemic arteries. PGI2 caused a small relaxation in control arteries and a small contraction in ischemic arteries. α-Adrenoceptors and COX-2 protein expression and the metabolite of PGI2 were augmented in ischemic arteries. Therefore, ischemia-reperfusion may increase the cerebrovascular responsiveness to noradrenaline, through upregulation of α-adrenoceptors and increased COX-2-derived PGI2 exerting a vasoconstrictor action. After ischemia-reperfusion, noradrenaline might increase PGI2 production thus contributing to adrenergic vasoconstriction and/or PGI2 would potentiate the noradrenaline effects.