Antenatal Betamethasone Alters Vascular Reactivity in Adult Female Ovine Cerebral Arteries

Abstract

Although the use of antenatal glucocorticoids has resulted in decreased neonatal morbidity/mortality, recent animal studies have raised concerns regarding adverse effects of these medications on postnatal cardiovascular function. We hypothesized that antenatal betamethasone (Beta) exposure alters cerebral vascular reactivity in adult female sheep. We observed that K+-induced constriction was comparable in middle cerebral artery (MCA) from Beta-exposed animals and age-matched controls. Pressure-induced constriction was significantly attenuated in MCA from Beta-exposed compared with control sheep. Inhibition of NOS significantly augmented pressure-induced constriction in MCA from both Beta-exposed and control sheep whereas cyclooxygenase (COX) inhibition augmented pressure-induced constriction only in MCA from Beta-exposed sheep. Furthermore, NOS and COX inhibition significantly attenuated bradykinin (BK)-induced dilation in MCA from both Beta-exposed and control sheep. However, there appeared to be a greater contribution of both NOS and COX to BK-induced dilation in Beta-exposed compared with control MCA. Our findings demonstrate that fetal exposure to a clinically relevant course of Beta alters cerebral vascular tone and reactivity in adult female sheep.

Maternal food restriction modulates cerebrovascular structure and contractility in adult rat offspring: effects of metyrapone

“…One of the possible mechanisms through which MFR could modulate multiple key vascular proteins is through activation of glucocorticoid receptors (19,42,51). Consistent with a role for glucocorticoids in MFR-induced changes in contractility, Metyrapone blocked the effects of MFR on potassium contractions at low (40 mmHg) and high (80 mmHg) pressures (Fig.…”

“…From this perspective, our data raise the possibility that gestational food restriction in the absence of glucocorticoids causes epigenetic changes in gene expression for calcium-regulating proteins and that glucocorticoids protect against such effects. Although glucocorticoids can produce long-term depression of contractility in cerebral arteries (19) and, over the short term, can inhibit myofilament sensitivity in airway smooth muscle (24) and uterine arteries (69), metyrapone had very little long-term effect on myofilament calcium sensitivity in cerebral arteries of MFR offspring (Fig. 2, bottom).…”

Pregnancy increases myometrial artery myogenic tone via NOS- or COX-independent mechanisms

“…All experiments were conducted in a manner similar to that previously described (7). Briefly, the cannulated arteries were initially pressurized to 20 mmHg and allowed to equilibrate for 20 min at 37°C.…”

Effect of perinatal glucocorticoids on vascular health and disease

“…In the kidney, renal blood flow in newborn preterm lambs is improved after single course antenatal BMZ but long-term assessment of these animals reveals an association between antenatal steroid exposure and hypertension and altered renal development in adult life that may be gender-specific (51)(52)(53). The adult cerebral circulation of prenatally-exposed sheep to clinically relevant doses of antenatal BMZ exhibits attenuation of pressure-induced vasoconstriction and altered vessel reactivity (54). Fetal programming upon exposure to high dose antenatal (or postnatal) corticosteroids undoubtedly influences the long-term impact of corticosteroids on the developing vascular system and is an important area for further animal and human research.…”