Blood-brain barrier permeability during dopamine-induced hypertension in fetal sheep

Dopamine is often used as a pressor agent in sick newborn infants, but an i ncrease in arterial blood pressure could disrupt the blood-brain barrier (B BB), especially in the preterm newborn. Using time-dated pregnant sheep, we tested the hypothesis that dopamine-induced hypertension increases fetal B BB permeability and cerebral water content. Barrier permeability was assess ed in nine brain regions, including cerebral cortex, caudate, thalamus, bra in stem, cerebellum, and spinal cord, by intravenous injection of the small tracer molecule [C-14] aminoisobutyric acid at 10 min after the start of d opamine or saline infusion. We studied 23 chronically catheterized fetal sh eep at 0.6 (93 days, n = 10) and 0.9 (132 days, n = 13) gestation. Intraven ous infusion of dopamine increased mean arterial pressure from 38 +/- 3 to 53 +/- 5 mmHg in 93-day fetuses and from 55 +/- 5 to 77 +/- 8 mmHg in 132-d ay fetuses without a decrease in arterial O-2 content. These 40% increases in arterial pressure are close to the maximum hypertension reported for phy siological stresses at these ages in fetal sheep. No significant increases in the brain transfer coefficient of aminoisobutyric acid were detected in any brain region in dopamine-treated fetuses compared with saline controls at 0.6 or 0.9 gestation. There was also no significant increase in cortical water content with dopamine infusion at either age. We conclude that a 40% increase in mean arterial pressure during dopamine infusion in normoxic fe tal sheep does not produce substantial BBB disruption or cerebral edema eve n as early as 0.6 gestation.