| Adrenomedullin relaxes rat uterine artery: mechanisms and influence of pregnancy and estradiol. | |
| | |
MedLine Citation:
|
PMID: 20631002 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Uterine arteries play a major role in regulating uteroplacental blood flow. Failure to maintain blood flow to the uteroplacental compartment during pregnancy often results in intrauterine growth retardation. Immunohistochemical staining of adrenomedullin (AM), an endogenous vasoactive peptide, in uterine artery was intense in pregnant compared to nonpregnant rats, but it is not known whether AM directly relaxes uterine artery or not. In this study, we elucidated the mechanisms of uterine artery relaxation by AM and its regulation by pregnancy and female sex steroids. AM was able to relax uterine artery, and this relaxation was influenced positively by pregnancy and estradiol as evidenced by the increased pD(2) and E(max) values of AM. Both pregnancy and estradiol treatment to ovariectomized rats amplified RAMP(3) expression in uterine arteries while progesterone had no effect. AM-induced uterine artery relaxation is predominantly endothelium-dependent. The AM receptor antagonist CGRP(8-37) is more potent than AM(22-52) in inhibiting the AM relaxation, indicating the involvement of AM(2) receptor subtype. Moreover, AM uses the classical nitric oxide-cyclic guanosine monophosphate pathway along with K(Ca) channels to mediate the vasodilatory effect in uterine artery. In conclusion, sensitivity of uterine artery to AM-induced relaxation is increased with pregnancy or estradiol treatment by increasing RAMP(3) expression, suggesting an important role for AM in regulating the uterine hemodynamics, probably maintaining uterine blood flow during pregnancy and in pre- and postmenopausal cardiovascular adaptation differences. |
| | |
Authors:
|
Gracious R Ross; Uma Yallampalli; Pandu R R Gangula; Luckey Reed; K Sathishkumar; Haijun Gao; Madhu Chauhan; Chandra Yallampalli |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-14 |
Journal Detail:
|
Title: Endocrinology Volume: 151 ISSN: 1945-7170 ISO Abbreviation: Endocrinology Publication Date: 2010 Sep |
Date Detail:
|
Created Date: 2010-08-25 Completed Date: 2010-10-04 Revised Date: 2011-09-13 |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: United States |
Other Details:
|
Languages: eng Pagination: 4485-93 Citation Subset: AIM; IM |
Affiliation:
|
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23284, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adrenomedullin
/
chemistry,
pharmacology* Animals Calcitonin Gene-Related Peptide / pharmacology Dose-Response Relationship, Drug Endothelium, Vascular / physiology Estradiol / pharmacology* Female Gene Expression / drug effects Glyburide / pharmacology Intracellular Signaling Peptides and Proteins / genetics Membrane Proteins / genetics Ovariectomy Peptide Fragments / pharmacology Potassium Channel Blockers / pharmacology Pregnancy Progesterone / pharmacology Rats Rats, Sprague-Dawley Receptor Activity-Modifying Proteins Reverse Transcriptase Polymerase Chain Reaction Uterine Artery / drug effects*, metabolism, physiology Vasodilation / drug effects* Vasodilator Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
|
HL-58144/HL/NHLBI NIH HHS; HL-72620/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Peptide Fragments; 0/Potassium Channel Blockers; 0/Receptor Activity-Modifying Proteins; 0/Vasodilator Agents; 10238-21-8/Glyburide; 119911-68-1/calcitonin gene-related peptide (8-37); 148498-78-6/Adrenomedullin; 50-28-2/Estradiol; 57-83-0/Progesterone; 83652-28-2/Calcitonin Gene-Related Peptide |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Hyperinsulinemia Precedes Insulin Resistance in Mice Lacking Pancreatic {beta}-Cell Leptin Signaling...
Next Document: Minireview: Organizational hypothesis: instances of the fingerpost.