Document Detail


The role of aldosterone in mediating the dependence of angiotensin hypertension on IL-6.
MedLine Citation:
PMID:  19812355     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Knockout (KO) of IL-6 has been shown to attenuate ANG II hypertension, and mineralocorticoid receptors (MR) have been reported to contribute to the increase in IL-6 during acute ANG II infusion. This study determined whether that MR action is sustained with chronic ANG II infusion and whether it plays a role in mediating ANG II hypertension. ANG II infusion (90 ng/min) increased plasma IL-6 from 1.6 +/- 0.6 to 22.7 +/- 2.2 and 19.9 +/- 3.2 pg/ml on days 7 and 14, respectively, and chronic MR blockade with spironolactone attenuated that only at day 7 (7.2 +/- 2.2 pg/ml). ANG II increased MAP (19 h/day with telemetry) approximately 40 mmHg, but in ANG II+spironolactone mice (25 or 50 mg*kg(-1)*day(-1)), mean arterial pressure (MAP) was not significantly different despite a tendency for lower pressure the first 6 days. To isolate further the mineralocorticoid link to IL-6 and blood pressure, DOCA-salt hypertension was induced in IL-6 KO and wild-type (WT) mice. Plasma IL-6 increased from 4.1 +/- 1.7 to 34.5 +/- 7.0 pg/ml by day 7 of DOCA treatment in the WT mice but was back to control levels by day 14. An IL-6 bioassay using the murine B9, B-cell hybridoma cell line demonstrated that plasma IL-6 measurements reflected actual IL-6 bioactivity. The hypertension was not different and virtually superimposable in WT vs. IL-6 KO mice, averaging 145 +/- 2 and 144 +/- 3 mmHg, respectively. Both experiments confirm chronic stimulation of IL-6 by mineralocorticoids but show that it is transient. In addition, IL-6 was not required for mineralocorticoid hypertension. This suggests that aldosterone contributes to the increase in plasma IL-6 in the early stage of ANG II hypertension but that the blood pressure actions of IL-6 in that model are linked most likely to ANG II rather than aldosterone.
Authors:
LaShon C Sturgis; Joseph G Cannon; Derek A Schreihofer; Michael W Brands
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-10-07
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  297     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-25     Completed Date:  2009-12-11     Revised Date:  2011-03-03    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1742-8     Citation Subset:  IM    
Affiliation:
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
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MeSH Terms
Descriptor/Qualifier:
Aldosterone / metabolism*
Aldosterone Antagonists / pharmacology
Angiotensins / administration & dosage
Animals
Antihypertensive Agents / pharmacology
Blood Pressure* / drug effects
Desoxycorticosterone
Disease Models, Animal
Hypertension / chemically induced,  drug therapy,  immunology,  metabolism*,  physiopathology
Infusion Pumps, Implantable
Infusions, Subcutaneous
Interleukin-6 / blood,  deficiency,  genetics,  metabolism*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Spironolactone / pharmacology
Time Factors
Grant Support
ID/Acronym/Agency:
HL56259/HL/NHLBI NIH HHS; HL74167/HL/NHLBI NIH HHS; HL75625/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Aldosterone Antagonists; 0/Angiotensins; 0/Antihypertensive Agents; 0/Interleukin-6; 52-01-7/Spironolactone; 52-39-1/Aldosterone; 64-85-7/Desoxycorticosterone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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