Development of fetal vascular responses to endothelin-1 and acetylcholine in the sheep

Responses to K+, endothelin-1 (ET-1), and acetylcholine (ACh) of isolated a drenal, femoral, middle cerebral, and renal arteries from fetal [110-145 da ys gestational age (dGA, term similar to 148 dGA)] and 0- to 24-h newborn ( NB) lambs were evaluated using the technique of wire myography. Responses a t distinct developmental ages for each vascular bed were compared. In all a rteries sensitivity to K+-induced vasoconstriction was similar at all fetal age points examined. In contrast, sensitivity to ET-1 increased with incre asing fetal age in arteries from all vascular beds. The magnitude of the ma ximal vasoconstriction was positively correlated with GA for K+ in adrenal, femoral, and cerebral arteries and for ET-1 in femoral, cerebral, and rena l arteries. Cerebral arteries showed a greater sensitivity when compared wi th the other systemic arteries to K+ and ET-1 at all fetal ages and to K+ i n NB. ACh evoked relaxatory responses in fetal and NB femoral and adrenal a rteries. However, renal arteries relaxed comparatively less in response to ACh, and no vasodilation was noted in middle cerebral arteries at any age p oints examined. For femoral arteries ACh-induced vasorelaxation decreased w ith increasing GA but was restored in arteries from NB lambs. In summary, t he responsiveness of isolated resistance arteries varies with developmental age in the fetal and perinatal sheep and these effects are both agonist an d vascular bed specific. The augmented sensitivity in response to ET-1 of m iddle cerebral compared with other systemic arteries may reflect the import ance of cerebral blood flow control during this critical developmental peri od.