Effect of Pregnancy and Sex Steroids on α₁‐Adrenoceptor Mechanisms in the Guinea‐Pig Uterine Vascular Bed

Abstract

Adrenoceptor mechanisms in the extrinsic uterine arteries from late pregnant guinea-pigs were characterized pharmacologically and compared with contractile responses of uterine arteries from non-pregnant and oophorectomized control, progesterone and oestrogen treated animals. Pregnancy caused an increase in diameter of the arteries, more pronounced the more distal they were. There was no change in potassium-evoked maximum contractions during pregnancy.Noradrenaline (10 nM to 1 mM), in the presence of cocaine (1 pM) and propranolol (0.1 pM), induced concentrationdependent contractions of the arterial segments, with approximately similar pD2 values. The maximum responses (Emax) were significantly increased during pregnancy and hormone supplementation. Prazosin (10 nM to 1 pM), but not rauwolscine (10 nM to 1 pM), antagonized noradrenaline-evoked contractions of the arteries. Isoprenaline (10 nM to 1 pM), in the presence of prazosin (0.1 pM) and cocaine (1 pM), had no relaxant effect on arteries contracted submaximally by prostaglandin Fz. ( 5 pM). Neither cocaine nor normetanephrine modified noradrenalhe-evoked contractions of the uterine artery. The results indicate that guinea-pig uterine vasoconstriction is mediated by a]-adrenoceptors while relaxant P-adrenoceptor effects, neuronal and extraneuronal uptake mechanisms are of minor importance. The observed increase in Em,, may be due either to an increase in the number of a]-adrenoceptors or to an enhanced pharmaco-mechanical coupling, which conceivably is regulated by sex steroids since this response was reproduced in castrated animals by hormone supplementation.

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

“…Nevertheless, experimental data from our study are very similar to those obtained with nonpregnant and pregnant human uterine radial arteries (Steele et al, 1993). In addition, the pD2 and maximal response values for non-pregnant and pregnant guinea-pig uterine artery with intact endothelium obtained from the present investigation are similar to those reported by Edvinsson (1986) andFallgren et al (1988).…”

“…This conclusion is consistent with the concept that in nonpregnant and pregnant guinea-pig uterine arteries with intact endothelium m-adrenoceptors are mainly of the ml subtype (Fallgren & Edvinsson, 1986;Fallgren et al, 1988 (Cocks & Angus, 1983;Lues & Schumann, 1984;Aloschie & Godfraind, 1988). It has been also demonstrated that in some blood vessels removal of endothelium enhanced receptor reserve for noradrenaline (Alosachie & Godfraind, 1988).…”

Decreased function of voltage-gated potassium channels contributes to augmented myogenic tone of uterine arteries in late pregnancy

“…These important changes occur in parallel with augmented responses of these vessels to some vasoconstrictors and to intraluminal pressure (12,14,35,48,59,61). The balance between augmented vasodilator and vasoconstrictor mechanisms determines uterine arterial tone and, consequently, blood flow to the placenta and fetus.…”

Diabetes and the maternal resistance vasculature

“…One possibility may be alterations in signal transduction pathways [84], which may account for the reduction of pressor responses to various vasoconstrictor agonists [85,86]. The increased synthesis and release of various endothelium-dependent relaxing factors, such as NO and PGI # [87,88], a decrease in the number of adrenergic receptors and a blunting of reflex cardiac responses [89,90] have also been implicated.…”