Characterisation of Tone Oscillations in Placental and Myometrial Arteries from Normal Pregnancies and Those Complicated by Pre-eclampsia and Growth Restriction

Abstract

Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur in vascular beds to allow acute regulation of volume flow and thus the delivery of oxygen and nutrients to the tissue. Mechanisms responsible for the control of human placental vasomotor tone and blood flow are poorly characterized. This study aimed to characterise thromboxane-induced tone oscillations in human placental and myometrial arteries. Chorionic plate and myometrial arteries obtained from biopsies at term were mounted for isometric tension measurement. Tone oscillations were observed in chorionic arteries only when exposed to sub-maximal (<1 μM) concentrations of U46619. Slow (mean ± SEM) frequency (2.6 ± 0.5 per hour), large amplitude (39 ± 7% of peak contraction) tone oscillations were elicited by 0.03 μM U46619 ( n = 18). In the presence of the nitric oxide synthase (NOS) inhibitor l-NNA (100 μM) the amplitude was significantly reduced (40 ± 13% to 18 ± 8%, P < 0.05, n = 6), frequency was unaltered and the bradykinin-dependent vasodilator response was reduced (68 ± 13% to 40 ± 19%, P < 0.05, n = 6). Myometrial arteries exposed to 1 μM U46619 developed tone oscillations within 10 min, which increased in amplitude over 30 min occurring at relatively constant frequency. The mean amplitude of oscillations at 30 min (31 ± 7%, n = 16) was similar to that in chorionic arteries but the occurrence more frequent (42.8 ± 9.7 per hour, P < 0.001). Inhibition of NOS did not alter tone oscillations in myometrial arteries. Tone oscillations in chorionic arteries from pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude whereas those in myometrial arteries had increased frequency. Inhibition of NOS further reduced oscillation amplitude in chorionic arteries from FGR pregnancies. The alterations may contribute to the vasculopathology of these conditions, or, may represent compensatory mechanisms to maintain a matching of materno-placental blood flow.