Effect of the vascular endothelium on noradrenaline-induced contractions in non-pregnant and pregnant guinea-pig uterine arteries.

Abstract

1. The effect of pregnancy on noradrenaline-mediated contraction of guinea-pig uterine artery rings with both intact and denuded endothelium was investigated. 2. Noradrenaline (25 nM-100 microM) induced concentration-dependent contraction of non-pregnant and pregnant guinea-pig uterine arterial rings with intact endothelium with similar pD2 and maximal response values (non-pregnant: pD2 = 5.85 +/- 0.02, maximal response = 121 +/- 8.2%; pregnant: pD2 = 5.81 +/- 0.04, maximal response = 122 +/- 9.1%). Removal of endothelium did not affect noradrenaline-induced contractions in non-pregnant guinea-pig uterine artery (pD2 = 5.97 +/- 0.02, maximal response = 119 +/- 8.6%). In contrast, in arteries from pregnant guinea-pigs, removal of endothelium shifted concentration-response curve for noradrenaline to the left, without affecting maximal response value (pD2 = 6.36 +/- 0.03, maximal response = 120 +/- 9.0%). 3. The pKA values for noradrenaline were: 5.76 +/- 0.09 and 5.82 +/- 0.10 for non-pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively and 5.74 +/- 0.09 and 5.72 +/- 0.07 for pregnant guinea-pig uterine artery with intact and denuded endothelium, respectively. 4. The receptor occupancy-response relationship for noradrenaline was linear for all types of vessels, except for pregnant guinea-pig uterine artery with denuded endothelium, since half-maximal response to noradrenaline was obtained with 44.8 +/- 6.9% (non-pregnant guinea-pig uterine artery with intact endothelium), 43.3 +/- 6.1% (non-pregnant guinea-pig uterine artery with denuded endothelium) and 44.3 +/- 6.3% (pregnant guinea-pig uterine artery with intact endothelium) receptor occupancy. In pregnant guinea-pig uterine artery with denuded endothelium, occupancy-response relationship for noradrenaline was non-linear since half-maximal response to noradrenaline was obtained with 19.7 +/- 3.3% receptor occupancy. 5. NG-monomethyl-L-arginine (100 microM) and indomethacin (10 microM) did not affect concentration-response curve for noradrenaline in guinea-pig uterine arteries, regardless of pregnancy status or endothelial condition. 6. In quiescent preparations, the alpha-adrenoceptor antagonists, prazosin (5-50 nM) and yohimbine (1-10 microM) produced parallel rightward shifts of the curves for noradrenaline and the slopes of the Schild plots were not significantly different from unity. The plots constrained to a slope of unity gave the following - log Kb values: prazosin vs. yohimbine 8.78 +/- 0.03 vs. 6.41 +/- 0.02 for non-pregnant guinea pig uterine artery with intact endothelium, 8.95 +/- 0.03 vs. 6.34 +/- 0.02 for non-pregnant guinea-pig uterine artery with denuded endothelium, 8.91 +/- 0.01 vs. 6.44 +/- 0.03 for pregnant guinea-pig uterine artery with intact endothelium and 9.07 +/- 0.01 vs. 6.52 +/- 0.03 for pregnant guinea-pig uterine artery with denuded endothelium.7. It is concluded that initially there is no difference in noradrenaline action between uterine arteries from non-pregnant and pregnant guinea-pigs, but after removal of the endothelium the pregnant guinea-pig uterine artery is more sensitive to noradrenaline, which is related to increased receptor reserve for noradrenaline in this tissue. It is probable that relaxing factor derived from the endothelium mediates this effect, but it is unlikely to be nitric oxide or prostacyclin. Antagonist affinities and affinity of noradrenaline itself suggests that an identical subtype of alpha-adrenoceptor, probably the alpha 1 subtype, is involved in the noradrenaline-induced contraction of non-pregnant and pregnant guinea-pig uterine artery with or without endothelium.