Pregnancy does not alter the response of uterine arteries to vasoactive intestinal polypeptide.
In order to provide sufficient nutrients for fetal development, pregnancy is associated with a significant increase in uterine blood flow. Although vasoactive intestinal polypeptide (VIP) is considered to be an important regulator of uterine blood flow it is not known whether endothelium-derived relaxing factors contribute to VIP action in the uterine artery, whether pregnancy alters the effect of VIP in the uterine artery and/or whether VIP interacts with noradrenaline and acetylcholine on the uterine artery and whether pregnancy regulates this possible interaction. In the present study, VIP induced a concentration-dependent relaxation of guinea pig uterine arterial rings, both intact and denuded of endothelium. Pregnancy did not alter the relaxation of uterine artery in response to VIP. In all preparations, addition of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin and diethylcarbamazine did not modify the effect of VIP in uterine arteries. The VIP-receptor complex dissociation constant did not differ significantly between studied vessels, and in all experimental groups the relationship between receptor occupancy and the response was linear, with the receptor reserve (K(A)/EC(50)) close to unity. VIP did not modulate acetylcholine-induced relaxation or noradrenaline-induced contraction in both non-pregnant and pregnant guinea pig uterine arteries. This study has shown that: (i) VIP induces relaxation of guinea pig uterine artery acting as a partial agonist on receptors localized in smooth muscle; (ii) pregnancy does not alter the response of guinea pig uterine arteries to VIP and does not change the receptor affinity for VIP, the efficiency of the receptor coupling or the VIP receptor density; and (iii) VIP does not modulate effects of neurotransmitters on guinea pig uterine arteries and pregnancy is not associated with the changes of VIP-neurotransmitter interaction.
Jovanovic
S
S
Tayside Institute of Child Health, University of Dundee, Ninewells Hospital & Medical School, Dundee, DD1 9SY, Scotland, UK.
Grbovic
L
L
Jovanovic
A
A
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004049:Diethylcarbamazine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism; D014599:Uterus / Q000098:blood supply*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism* / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D016859:Lipoxygenase Inhibitors; D018005:Receptors, Vasoactive Intestinal Peptide; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; D014660:Vasoactive Intestinal Peptide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D004049:Diethylcarbamazine; D009638:Norepinephrine; D007213:Indomethacin