title: Chronic exposure to low doses of estradiol-17ß increases blood pressure in young female rats: A possible role for central Endothelin-1.
abstract: Previously, we demonstrated that chronic exposure to low levels of estradiol-17β (E2) increases mean arterial pressure (MAP) in young female Sprague-Dawley (SD) rats, however, the underlying mechanisms are unclear. Since endothelin-1 (ET-1) is implicated in blood pressure (BP) regulation, we hypothesized that E2's effects on MAP are mediated through central ET-1. To test this, young female SD rats were either sham implanted or implanted s.c. with slow-release E2 pellets (20 ng/day for 90 days). BP was monitored by telemetry. After 75 days of E2 exposure, ETAantagonist or vehicle was administered i.c.v. After 90 days of E2 exposure, rats were sacrificed, and the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) were microdissected for gene expression and protein analysis of ET-1 and its receptors. E2 exposure increased MAP after pellet implantation. Gene expression of ET-1 and ETAbut not ETBreceptors were upregulated in the PVN and RVLM of E2 treated animals. Further, the protein levels of ETAreceptor were also increased in the PVN of E2 treated animals. However, i.c.v. infusion of the ETAantagonist did not completely block the increase in blood pressure. Our results suggest that increases in central ET-1 activity could possibly play a role in chronic E2-induced increase in BP but further studies are needed to completely understand the contribution of ET-1 in this phenomenon.
authors.affiliation: Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Madhan
authors.initials: M
authors.lastname: Subramanian
authors.affiliation: Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA, 30602, USA.|Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Sheba M J
authors.initials: SM
authors.lastname: MohanKumar
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Priya
authors.initials: P
authors.lastname: Balasubramanian
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Northcott
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Garver
authors.affiliation: Department of Pharmacology & Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
authors.affiliation: Department of Pathobiology & Diagnostic Investigation, Michigan State University, East Lansing, MI, 48824, USA. psmohan@uga.edu.|Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA, 30602, USA. psmohan@uga.edu.
authors.forename: P S
authors.initials: PS
authors.lastname: MohanKumar
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism*; D004958:Estradiol / Q000633:toxicity*; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D008526:Medulla Oblongata / Q000737:chemistry / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011959:Receptors, Estradiol / Q000235:genetics / Q000378:metabolism; D036401:Toxicity Tests, Chronic
chemical_list: D019332:Endothelin-1; D004965:Estrogen Antagonists; D011959:Receptors, Estradiol; D004958:Estradiol