The role of extracellular calcium in pregnancy-induced attenuation of phenylephrine contraction in rat aorta with functional endothelium

Abstract

The effect of pregnancy on the supply of calcium ions for the contractile responses of rat aortic rings to phenylephrine was investigated. The contractility of intact aortic rings from pregnant rats, compared with that of similar rings from non-pregnant rats, to phenylephrine and potassium chloride was significantly decreased. Contractions of rings from non-pregnant rats, pretreated with phenylephrine or potassium chloride, in response to calcium chloride were greater than those of similarly treated rings from pregnant rats. When the concentration of calcium chloride in the medium bathing the rings was reduced to 0.8 mmol.l-1, the contractile response to phenylephrine was significantly (P < 0.005) inhibited in rings from both pregnant and non-pregnant rats but to a greater extent in rings from non-pregnant rats. Contractions of aortic rings from pregnant rats in response to phenylephrine in calcium-free medium were similar to those of rings from non-pregnant rats, suggesting equal dependence on calcium from intracellular stores. The results suggest that pregnancy decreased the response to calcium influx into the aortic smooth muscle cells through both receptor- and voltage-operated calcium entry pathways. Since de-endothelialization reversed the pregnancy-induced diminished contraction to phenylephrine, it is likely that pregnancy interfered with contractions induced by activation of receptors with phenylephrine through enhanced production of endothelium-derived relaxing factor(s).

The effect of sodium based hypo-osmolality on arterial smooth muscle reactivity in vitro

“…The mechanisms involved are similar in some respects to those described for tissues from normal pregnancy in that they are endothelium-dependent, involve enhanced relaxation to acetylcholine and increased activity of the Na + -K + ATPase, are not affected by treatment with indomethacin and do not involve changes in intracellular release of calcium. However, unlike the observations previously reported for normal pregnancy [17,19], the contractile responses to KCl were not significantly diminished, and the responses to CaCl 2 were unaltered. The nonpregnant source of the tissue may explain the differences.…”

“…We have previously reported that, in vitro, the mechanisms of attenuated vascular response in pregnancy involve the vascular endothelium [15] and include enhanced acetylcholine-induced relaxation [16], increased functional activity of the Na + /K + ATPase [5], reduced extracellular influx of calcium reduced with no change in intracellular release of calcium [17], and insensitivity to indomethacin [15,16]. This study investigated the possibility that these changes could be duplicated in aortic rings from nonpregnant rats, exposed to mild hypo-osmolarity achieved by manipulation of [Na + ] e , and therefore provide an explanation for the attenuated vascular reactivity in normal pregnancy.…”

The alterations of vascular smooth muscle reactivity in vitro by human chorionic gonadotrophin

“…*** P < 0.0001, ** P < 0.01 Vascular reactivity is modulated by the endothelium through the production of vasodilators, such as nitric oxide, prostacyclin, endothelium-derived hyperpolarising factor and vasoconstrictors, such as endothelium-derived constricting factor, endothelin and thromboxane [8]. In normal pregnancy, there is endothelium-dependent attenuation of vascular reactivity, which involves enhanced production of vasodilators [1,2,7,21]. However, the contractionattenuating effect of hCG is unlikely to be the result of increased production of nitric oxide, since the application of L-NMMA in this study (to block nitric oxide synthase) did not normalise the contractile responses to phenylephrine.…”

Enhanced vascular effects of the Ca2+channel agonist Bay K 8644 in pregnant rabbits

“…The mechanism of the pregnancy-induced decrease of vascular pressor responsiveness to these hormones has not yet been clarified. Downregulation of specific receptors (2,13,18), enhanced secretion of vasodilatory substances (9), and alterations of receptor-response coupling (uncoupling) (8,11,28,29,34) have been considered as mediators of decreased vasopressor response to these hormones.…”

“…A gestational alteration of the vascular L-VDCC has already been suggested. For example, activation of the channel as induced by depolarization or Bay K 8644 (BAY), a specific L-VDCC agonist (31), was observed to be a less potent signal for vascular constriction in aortic rings and mesenteric arteries of pregnant than nonpregnant rats (11,28,29,34). In addition, chronic estrogen administration was noted to decrease the number of L-VDCC (26).…”