Effects of endothelial cell removal on constrictor and dilator responses of aortae of pregnant rats

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Abstract
1 The possibility has been examined that changes in sensitivity of the aorta occurring during pregnancy in the rat are due to changes in output of endothelium-derived relaxing factor (EDRF). 2 Concentration-isometric response curves, obtained in vitro, from thoracic aortic rings of non-pregnant rats in oestrous and 20-day pregnant rats to noradrenaline (NA) and phenylephrine (PE) were shallower with lower maxima when compared to those obtained to the thromboxane A2-mimetic U46619. 3 Removal of endothelium from aortae of non-pregnant animals caused significant shifts to the left of the curves obtained using all three agonists. In the case of NA or PE, EC50 values were reduced approximately fourfold, with maximum responses also increasing significantly. Endothelial cell removal caused an approximately eightfold increase in sensitivity to U46619 but no change in maximum response. The presence of oxyhaemoglobin (Hb) had a similar effect to endothelial removal on responses to NA and PE. 4 Rings obtained from 20-day pregnant rats showed significantly increased maximum responses to NA and PE when compared with those fron nonpregnant animals. Removal of the endothelium or the presence of Hb caused significant shifts of the dose-response curves to the left and further increases in maxima. 5 In contrast, no difference in maximum responses to U46619 could be detected between the aortic rings of pregnant and non-pregnant animals. Removal of the endothelium from either caused increases in sensitivity which did not differ significantly. 6 Relaxant responses to acetylcholine (ACh, 5 and 50 nM) of rings preconstricted with U46619 were greater in those from pregnant than from non-pregnant animals. However, when rings were preconstricted approximately 80-90% of maximum with NA or PE, no change in sensitivity to ACh was seen between the two groups of animals when its relaxant effect was expressed as a percentage of the response to the constricting agent. 7 These results indicate that the aorta shows in vitro supersensitivity, measured as an increase in maximum response, to .alpha.-adrenoreceptor agonists at the terminal stage of pregnancy in the rat. The data obtained using ACh suggests that either the supersensitivity is not due to reduced output of EDRF, or, alternatively, changes in its production induced by NA and PE can occur without analogous changes in ACh-stimulated output. Normal sensitivity of aortae from both pregnant and non-pregnant animals to the constrictor agents is endothelium-dependent.