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

Abstract

Responses to K(+), endothelin-1 (ET-1), and acetylcholine (ACh) of isolated adrenal, femoral, middle cerebral, and renal arteries from fetal [110--145 days gestational age (dGA, term approximately 148 dGA)] and 0- to 24-h newborn (NB) lambs were evaluated using the technique of wire myography. Responses at distinct developmental ages for each vascular bed were compared. In all arteries sensitivity to K(+)-induced vasoconstriction was similar at all fetal age points examined. In contrast, sensitivity to ET-1 increased with increasing fetal age in arteries from all vascular beds. The magnitude of the maximal vasoconstriction was positively correlated with GA for K(+) in adrenal, femoral, and cerebral arteries and for ET-1 in femoral, cerebral, and renal arteries. Cerebral arteries showed a greater sensitivity when compared with the other systemic arteries to K(+) and ET-1 at all fetal ages and to K(+) in NB. ACh evoked relaxatory responses in fetal and NB femoral and adrenal arteries. However, renal arteries relaxed comparatively less in response to ACh, and no vasodilation was noted in middle cerebral arteries at any age points examined. For femoral arteries ACh-induced vasorelaxation decreased with increasing GA but was restored in arteries from NB lambs. In summary, the responsiveness of isolated resistance arteries varies with developmental age in the fetal and perinatal sheep and these effects are both agonist and vascular bed specific. The augmented sensitivity in response to ET-1 of middle cerebral compared with other systemic arteries may reflect the importance of cerebral blood flow control during this critical developmental period.

Vascular development in early ovine gestation: carotid smooth muscle function, phenotype, and biochemical markers

“…Thus SMC of different embryological origins and from different vascular beds may have specific developmental patterns (27,53,55). Similar to the study of Hai et al (25), which began at 106 -108 days of gestation, most studies of VSM development and function have been limited to the last third of gestation, i.e., Ͼ100 days of gestation, and have been predominantly near term (17,45).…”

“…Thus observations of VSM function and maturation during development are likely to be specific to the vascular bed under study, and results cannot be generalized. Furthermore, this has not been thoroughly examined early in development.Maturational changes in VSM function are associated with changes in cellular protein expression in near term and newborn animals (6,11,17,43); however, this is not described in midgestation, e.g., Ͻ100 days gestation in the sheep and Յ28 wk in the human. Recent clinical advances have resulted in survival of neonates born at Յ28 wk (33).…”

“…Maturational changes in VSM function are associated with changes in cellular protein expression in near term and newborn animals (6,11,17,43); however, this is not described in midgestation, e.g., Ͻ100 days gestation in the sheep and Յ28 wk in the human. Recent clinical advances have resulted in survival of neonates born at Յ28 wk (33).…”

Development of the ovine fetal cardiovascular defense to hypoxemia towards full term

“…Studies in our laboratory have shown that treatment of immature fetal sheep with dexamethasone enhances the magnitude of the femoral vasoconstrictor response to acute hypoxemia to values obtained in fetuses at full term (22). Studies using in vitro wire myography have demonstrated developmental changes in the sensitivity and responsiveness of isolated ovine fetal resistance arteries to vasoconstrictor and vasodilator agents (15,16). Although vascular sensitivity to NE declined in the ovine fetal middle cerebral and femoral arteries, the magnitude of the maximum femoral arterial contractile response elicited by NE increased with advancing gestational age (15).…”

Maternally Administered Dexamethasone at 0.7 of Gestation Suppresses Maternal and Fetal Pituitary and Adrenal Responses to Hypoxemia in Sheep

“…In this study, we found that maternal DM treatment resulted in fetal hypertension that was short-lived and diminished with subsequent injections. We have investigated the peripheral mechanisms by which glucocorticoids increase BP and have demonstrated an increase in vasoconstriction of small resistance arteries in the fetal sheep in response to endothelin as the fetus matures during the final third of gestation (50), which is mimicked by administration of DM directly to the fetus (51). However, in the adult rat, the pressor effects of ACTH are not ameliorated by endothelin-1 antagonism with bosetan (52).…”