Overview

This dissertation, Mechanisms of Acute Actions of 17B-estradiol in the Vascular System by Wen-yee, Wendy, Keung, 姜韻兒, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Mechanisms of Acute Actions of 17β-Estradiol in the Vascular System Submitted by Wendy Wen Yee Keung for the degree of Master of Philosophy at the University of Hong Kong in December 2001 Epidemiological studies reveal that pre-menopausal women enjoy a lower incidence of cardiovascular diseases over men. This has been attributed, in part, to the cardioprotective effects of the female sex hormone estrogen. Conventionally, it is believed that the cardioprotective effects of estrogen are achieved via its long-term actions, through the modulation of gene transcription and its antioxidant effects. However, it has been observed that these effects together cannot account for the overall cardioprotective effects of estrogen. It has thus been suggested that estrogen also exerts acute effect on the vasculature. The objective of the present study is to attempt to elucidate the mechanisms of acute effects of estrogen in the vascular system, using the porcine coronary artery as a model system for study. Acute exposure to 17β-estradiol impaired agonist-induced contraction in isolated porcine coronary arteries in vitro, regardless of the presence or absence of an intact endothelium. Effect of 17β-estradiol was sensitive to blockade by the adenylyl icyclase inhibitor, SQ 22536, and the competitive antagonist of adenosine-3',5'- cyclic monophosphate (cAMP), Rp-8-Br-cAMPS. These findings suggest that 17β- estradiol acts via an activation of adenylyl cyclase and an increase in cAMP production. The effect of 17β-estradiol was found to be insensitive to guanylyl cyclase inhibitors. However, both the competitive antagonist of guanosine-3',5'-cyclic monophosphate (cGMP), Rp-8-Br-cGMPS, and protein kinase G antagonists were able to inhibit the effect of 17β-estradiol, suggesting that activation of protein kinase G is probably alsoinvolved in this acute vascular effect of 17β-estradiol. Administration of both cAMP and cGMP analogues elicited an impairment of contraction in porcine coronary arteries. The effect was effectively inhibited by the opposing competitive cyclic nucleotide antagonist, demonstrating the existence of cross-activation between the two cyclic nucleotide cascades in the vascular smooth muscle. Taken together, these findings suggest that 17β-estradiol acts by activating adenylyl cyclase in the vascular smooth muscle, increasing the production of cAMP, which then cross-activates protein kinase G that acts to diminish contraction in porcine coronary arteries. In summary, the present study have depicted a possible mechanism of the acute action of 17β-estradiol observed in porcine coronary arteries in vitro, which may contribute to increasing the understanding of the overall cardioprotective effects observed in women. (359 words) ii DOI: 10.5353/th_b2969748 Subjects: EstradiolBlood-vessels

Full Product Details

9781374713840

Table of Contents

Reviews

Author Information

Tab Content 6

Countries Available