INFLUENCE OF HYPOXIA ISCHEMIA ON CEREBROVASCULAR RESPONSES TO OXYTOCIN IN PIGLETS/

We examined the effects of hypoxic/ischemic stress on cerebral arterio lar responses to oxytocin in anesthetized piglets. Pial arteriolar dia meters were measured using a cranial window and intravital microscopy. First, we evaluated arteriolar responses to topical application of ox ytocin during normoxic conditions. We then determined whether 5-10 min of arterial hypoxia, ischemia, or asphyxia alters oxytocin-induced re sponses. Arterial hypoxia was produced by inhalation of 7.5% O-2-92.5% N-2 for 10 min. Ischemia was achieved by increasing intracranial pres sure for 10 min. Asphyxia was achieved by turning off the ventilator f or 5 min. During normoxic conditions, oxytocin dilated pial arterioles by 9 +/- 1% at 10(-8) and by 16 +/- 1% at 10(-6) mol/l (n = 47, p < 0 .05). Arteriolar responses to oxytocin did not change with repeated ap plications (n = 10). Following hypoxia, dilator effect of oxytocin was not changed at 10(-8) (8 +/- 2%) but it was reduced at 10(-6) mol/l ( 7 +/- 2%; p < 0.05, n = 8). After asphyxia or ischemia, oxytocin did n ot dilate arterioles at 10(-8) mol/l, whereas 10(-6) mol/l resulted in a mild vasoconstriction (-4 +/- 3 to -6 +/- 4%, n = 6 and 8). Topical ly applied superoxide dismutase did not preserve arteriolar responses to oxytocin after asphyxia although the arterioles did not constrict t o 10(-6) mol/l oxytocin (n = 5). Dilatation of cerebral arterioles in response to oxytocin was reversed to constriction by N-omega-nitro-L a rginine methyl ester (L-NAME)(15 mg/kg, i.v.; n = 5) and by endothelia l impairment by intra-arterial infusion of phorbol ester (10(-5) mol/l ; n = 5). We conclude that the absence of pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates endothelial dysfunction which may be involved in the pathology of perinatal brain injury.