Date of Graduation

1997

Document Type

Dissertation/Thesis

Abstract

This dissertation is composed of two topics that share the focus of placental vascular tone control. In the first investigations, we looked at the effect of caffeine (Caff; 10nmol/L-10{dollar}\\mu{dollar}mol/L), nicotine (Nic), and cotinine (Cot) (1nmol/L-100{dollar}\\mu{dollar}mol/L for both) administration on isolated placental blood vessels, to see if these substances altered placental vascular tone. We found that moderate relaxations were initiated by all three alkaloids in precontracted placental blood vessels. We also found that pretreatment of placental blood vessels and Caff, Nic, and Cot did not alter responses to a variety of contractile agents. In conclusion, it would seem that the adverse effects of maternal caffeine and nicotine use are unlikely to be mediated by alterations in placental vascular tone. In the second series of studies, we first found that physiological levels of progesterone (P) (0.01-{dollar}\\rm 30\\mu mol/L){dollar} caused endothelium-independent, receptor mediated and possibly cAMP dependent relaxations in precontracted placental blood vessels. In the next set of studies, we found that not only P but also three of its metabolites {dollar}(5\\beta{dollar}-Pregnane-3, 20-Dione, {dollar}5\\alpha{dollar}-Pregnane-3,20-Dione, or {dollar}5\\alpha{dollar}-Pregnan-{dollar}3\\beta{dollar}-Ol-20-One) also caused relaxations in preconstricted placental, as well as umbilical blood vessels at the same concentrations. The most potent of the three progestins was {dollar}5\\beta{dollar}-Pregnane-3,20-Dione but not as potent as P, while {dollar}5\\alpha{dollar}-Pregnane-3,20-Dione appeared to be the weakest. In the final two investigations, we found that this P-induced relaxation was significantly reduced in placental blood vessels from pregnancies complicated by HELLP syndrome and gestational diabetes. Relaxations to other known vasodilatory agents were not altered. Thus, indicative of intact relaxant mechanisms present in this circulation. Based on the results from the remaining four studies on P, it would seem that the relaxation in the placental circulation may be of physiological importance in maintaining adequate blood flow to the developing fetus. Additionally, P metabolites may play a role in the maintenance of placental blood flow, although P appeared to be the most potent. Finally, this relaxation to P is reduced in placental blood vessels complicated by HELLP syndrome and GDM, and this might contribute to the reported vasospasm and decreased placental blood flow in these complications of pregnancy.

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