Effects of Parturition on Estrogen Signaling in Resistance Arteries

Hdl Handle:
http://hdl.handle.net/10675.2/317706
Title:
Effects of Parturition on Estrogen Signaling in Resistance Arteries
Authors:
Royal, Crista Ruth
Abstract:
Few studies have examined the potential effects of childbirth on the responses of the female vasculature – especially the resistance microvasculature of non-reproductive tissues. We investigated the response of mesenteric microvascular resistance vessels to 17β-estradiol (E2), an important vasoactive hormone. Vessels were obtained from either nulliparous or postpartum female Sprague-Dawley rats, and isometric tension studies were performed. We found that E2 induced a concentration-dependent, endotheliumindependent relaxation of microvessels precontracted with 10-5M phenylephrine; however, E2-induced relaxation was reduced by nearly half in vessels from postpartum animals compared to nulliparous controls. Inhibiting nitric oxide synthase activity with 10-4M L-NMMA attenuated the relaxation effect of E2 on arteries from nulliparous animals. In contrast, L-NPA (which exhibits selectivity for type 1 or nNOS) had little effect on arteries from postpartum animals, suggesting a reduced influence of nNOS after parturition. Moreover, expression of nNOS protein in microvessels was decreased 39% in the postpartum state compared to arteries from nulliparous animals. We propose that the impaired E2-induced relaxation response of microvessels from postpartum animals reflects a downregulation of NO production due to lower nNOS expressed in vascular smooth muscle cells. We measured a 73% decrease in serum E2 levels in the postpartum state compared to nulliparous animals. Because E2 has been shown to increase nNOS protein expression, we propose that lower E2 levels after parturition decrease expression of nNOS, leading to a reduced vasodilatory capacity of resistance microvessels. Impaired E2-induced relaxation in resistance arteries from postpartum rats could also be restored by inhibiting COX with indomethacin (E2 300 nM 23.5±8.9% n=5) and even more profoundly with COX-2 inhibitor celecoxib (E2 300 nM 33.9±5.5% n=8). However, many women artificially increase estrogen levels soon after giving birth by taking oral contraceptives. Little is known regarding how parturition affects estrogen signaling, especially in resistance arteries, which can contribute to blood pressure regulation. We found that inhibiting COX-2 restored E2-induced vasodilation in arteries from postpartum rats.
Affiliation:
Department of Pharmacology and Toxicology
Issue Date:
Apr-2011
URI:
http://hdl.handle.net/10675.2/317706
Additional Links:
http://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/884648739?accountid=12365
Type:
Dissertation
Language:
en_US
Appears in Collections:
Theses and Dissertations; Department of Pharmacology and Toxicology Theses and Dissertations

Full metadata record

DC FieldValue Language
dc.contributor.authorRoyal, Crista Ruthen
dc.date.accessioned2014-06-02T15:02:06Z-
dc.date.available2014-06-02T15:02:06Z-
dc.date.issued2011-04-
dc.identifier.urihttp://hdl.handle.net/10675.2/317706-
dc.description.abstractFew studies have examined the potential effects of childbirth on the responses of the female vasculature – especially the resistance microvasculature of non-reproductive tissues. We investigated the response of mesenteric microvascular resistance vessels to 17β-estradiol (E2), an important vasoactive hormone. Vessels were obtained from either nulliparous or postpartum female Sprague-Dawley rats, and isometric tension studies were performed. We found that E2 induced a concentration-dependent, endotheliumindependent relaxation of microvessels precontracted with 10-5M phenylephrine; however, E2-induced relaxation was reduced by nearly half in vessels from postpartum animals compared to nulliparous controls. Inhibiting nitric oxide synthase activity with 10-4M L-NMMA attenuated the relaxation effect of E2 on arteries from nulliparous animals. In contrast, L-NPA (which exhibits selectivity for type 1 or nNOS) had little effect on arteries from postpartum animals, suggesting a reduced influence of nNOS after parturition. Moreover, expression of nNOS protein in microvessels was decreased 39% in the postpartum state compared to arteries from nulliparous animals. We propose that the impaired E2-induced relaxation response of microvessels from postpartum animals reflects a downregulation of NO production due to lower nNOS expressed in vascular smooth muscle cells. We measured a 73% decrease in serum E2 levels in the postpartum state compared to nulliparous animals. Because E2 has been shown to increase nNOS protein expression, we propose that lower E2 levels after parturition decrease expression of nNOS, leading to a reduced vasodilatory capacity of resistance microvessels. Impaired E2-induced relaxation in resistance arteries from postpartum rats could also be restored by inhibiting COX with indomethacin (E2 300 nM 23.5±8.9% n=5) and even more profoundly with COX-2 inhibitor celecoxib (E2 300 nM 33.9±5.5% n=8). However, many women artificially increase estrogen levels soon after giving birth by taking oral contraceptives. Little is known regarding how parturition affects estrogen signaling, especially in resistance arteries, which can contribute to blood pressure regulation. We found that inhibiting COX-2 restored E2-induced vasodilation in arteries from postpartum rats.en
dc.language.isoen_USen
dc.relation.urlhttp://ezproxy.gru.edu/login?url=http://search.proquest.com/docview/884648739?accountid=12365en
dc.rightsCopyright protected. Unauthorized reproduction or use beyond the exceptions granted by the Fair Use clause of U.S. Copyright law may violate federal law.-
dc.subjectParturitionen
dc.subjectEstrogenen
dc.subjectnNOSen
dc.subjectCOX-2en
dc.subjectMesenteric Arteriesen
dc.titleEffects of Parturition on Estrogen Signaling in Resistance Arteriesen
dc.typeDissertationen
dc.contributor.departmentDepartment of Pharmacology and Toxicologyen
dc.description.advisorWhite, Richard-
dc.description.committeeNot Listed-
dc.description.degreeDoctor of Philosophy (Ph.D.)-
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