Inhibitory Effects of Nitrendipine on Myometrial and Vascular Smooth Muscle in Human Pregnant Uterus and Placenta

Abstract

Human myometrial visceral and vascular preparations and placental chorionic and stem villous vessels were dissected from myometrial and placental specimens obtained at term Caesarean section and after vaginal delivery. Vascular ring preparations and myometrial strips were mounted in organ bath and isometric tension recorded. Only myometrial preparations developed spontaneous contractile activity, which was effectively blocked by the calcium channel blocker nitrendipine (NTD) 10−7M. Pretreatment with calcium‐depleted medium for 30 min. almost abolished myometrial responses to high K+ (124 mmol), oxytocin (OX) and prostaglandin F2a (PGF2a). Vascular responses to high K+ (124 mmol) were also nearly abolished by such treatment. However, noradrenaline (NA), vasopressin (VP) and PGF2a in myometrial arteries and PGF2a in chorionic vessels and stem villous arteries induced significant, but reduced contractions after calcium depletion. In all vascular preparations, exposed to calcium‐depleted medium, NTD (10−8M) almost abolished contractions induced by calcium (0.1–4.0 mM) in the presence of K+ (124 mmol) and depressed responses to calcium in the presence of the other agonists tested. NTD (10−10–10−7M) depressed myometrial contractions induced by K+, OX and PGF2a more effective than vascular responses to K+, NA, VP and PGF2a in the myometrial arteries and K+ and PGF2a in the placental arteries. It is concluded that activation of contraction in vessels from the human utero‐placental unit implies multiple cellular sources of calcium, while in myometrial smooth muscle, influx of superficially bound calcium may be an important initial step in contractile activation. Treatment with calcium channel blockers during late human pregnancy might involve relaxation of the myometrium together with vasodilatation of the myometrial and foetal placental vascular beds.

Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics

“…The effect of nifedipine on human myometrial strips was more marked in term not-in-labor than in term-labor specimens [43]. A significant proportion of oxytocin and PGF2α-induced contractions and increases in [Ca 2+ ] i in late pregnant guinea pig myometrium was attributed to Ca 2+ entry inhibited by L-type Ca blockers [44], as was the response in pregnant rat myometrial cell [45]. In contrast, no effect of nifedipine on oxytocin-stimulated increases in [Ca 2+ ] i was observed in nonpregnant human myometrial cells [46], and L-type blockers had no effect on oxytocin-stimulated PI turnover [2,47].…”

A computational model of excitation and contraction in uterine myocytes from the pregnant rat

“…Figure 12 maps out the effect of simultaneous alterations of g CaL and g Na on the intracellular Ca 2+ concentration. In the g CaL -g Na parameter space, changing the g CaL and g Na parameters from the bottom left hand corner to the top right resulted in an increase in [Ca 2+ ] i , which is analogous to the increased force shown over the course of gestation 43 , 44 . A variant combination of changes in the g CaL and g Na parameters affects the rate of change of cell activity.…”