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PMID: 17346686 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Dehydroepiandrosterone upregulates soluble guanylate cyclase and inhibits hypoxic pulmonary hypertension.

Cardiovascular research ·Vol. 74 ·No. 3 ·2007-06-01 ·Pages 377-87

Oka M, Karoor V, Homma N, Nagaoka T, Sakao E, Golembeski SM, Limbird J, Imamura M, Gebb SA, Fagan KA, McMurtry IF

Abstract

It has been reported that dehydroepiandrosterone is a pulmonary vasodilator and inhibits chronic hypoxia-induced pulmonary hypertension. Additionally, dehydroepiandrosterone has been shown to improve systemic vascular endothelial function. Thus, we hypothesized that chronic treatment with dehydroepiandrosterone would attenuate hypoxic pulmonary hypertension by enhancing pulmonary artery endothelial function. Rats were randomly assigned to five groups. Three groups received food containing 0, 0.3, or 1% dehydroepiandrosterone during a 3-wk-exposure to simulated high altitude (HA). The other 2 groups were kept at Denver's low altitude (LA) and received food containing 0 or 1% dehydroepiandrosterone. Dehydroepiandrosterone dose-dependently inhibited hypoxic pulmonary hypertension (mean pulmonary artery pressures after treatment with 0, 0.3, and 1% dehydroepiandrosterone=45+/-5, 33+/-2*, and 25+/-1*# mmHg, respectively. *P<0.05 vs. 0% and # vs. 0.3%). Dehydroepiandrosterone (1%, 3 wks) treatment started after rats had been exposed to 3-wk hypoxia also effectively reversed established hypoxic pulmonary hypertension. Pulmonary artery rings isolated from both LA and HA rats treated with 1% dehydroepiandrosterone showed enhanced relaxations to acetylcholine and sodium nitroprusside, but not to 8-bromo-cGMP. In the pulmonary artery tissue from dehydroepiandrosterone-treated LA and HA rats, soluble guanylate cyclase, but not endothelial nitric oxide synthase, protein levels were increased. These results indicate that the protective effect of dehydroepiandrosterone against hypoxic pulmonary hypertension may involve upregulation of pulmonary artery soluble guanylate cyclase protein expression and augmented pulmonary artery vasodilator responsiveness to nitric oxide.

MeSH Terms
Acetylcholine/pharmacology Animals Blotting, Western Cyclic GMP/pharmacology Dehydroepiandrosterone/metabolism,therapeutic use Dehydroepiandrosterone Sulfate/blood,metabolism Dose-Response Relationship, Drug Drug Administration Schedule Estradiol/blood Guanylate Cyclase/analysis,metabolism Hypertension, Pulmonary/blood,drug therapy,metabolism Hypoxia/metabolism In Vitro Techniques Lung/enzymology Male Muscle, Smooth, Vascular/metabolism Nitric Oxide/metabolism Nitric Oxide Synthase Type III/analysis,antagonists & inhibitors Nitroprusside/pharmacology Pulmonary Artery/drug effects,metabolism,physiopathology Random Allocation Rats Rats, Sprague-Dawley Receptors, Cytoplasmic and Nuclear/analysis,metabolism Soluble Guanylyl Cyclase Testosterone/blood Up-Regulation Vasodilator Agents/pharmacology
Chemicals
Receptors, Cytoplasmic and Nuclear Vasodilator Agents Nitroprusside Nitric Oxide Testosterone Dehydroepiandrosterone Estradiol Dehydroepiandrosterone Sulfate Nitric Oxide Synthase Type III Guanylate Cyclase Soluble Guanylyl Cyclase Cyclic GMP Acetylcholine
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Oka Masahiko
Cardiovascular Pulmonary Research Laboratory, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver Colorado 80262, United States. [email protected]
Karoor Vijaya
Homma Noriyuki
Nagaoka Tetsutaro
Sakao Eiko
Golembeski Scott M
Limbird Jennifer
Imamura Masatoshi
Gebb Sarah A
Fagan Karen A
McMurtry Ivan F
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Article Info
Journal
Cardiovascular research
Abbr.
Cardiovasc Res
ISSN
0008-6363
DOI
10.1016/j.cardiores.2007.01.021
Email
[email protected]
Published
2007-06-01
Epub
2007-00-12
Pages
377-87
Language
English
Region
England
NLM ID
0077427
PMCID
PMC1950784
Subset
IM
Grants
NHLBI NIH HHS · HL 14985 · United States
NHLBI NIH HHS · T32 HL007171 · United States
NHLBI NIH HHS · T32 HL007171-30 · United States
NHLBI NIH HHS · P01 HL014985 · United States
NHLBI NIH HHS · P01 HL014985-31 · United States
NHLBI NIH HHS · P01 HL014985-33 · United States
NHLBI NIH HHS · HL 07171 · United States
Corrections
CommentIn
PMID: 17466961
External Links
PubMed source DOI: 10.1016/j.cardiores.2007.01.021 PMC Full Text View journal details
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