The role of aldosterone in mediating the dependence of angiotensin hypertension on IL-6

La Shon C. Sturgis, Joseph G. Cannon, Derek A. Schreihofer, Michael W. Brands

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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) ∼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.

Original languageEnglish (US)
Pages (from-to)R1742-R1748
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume297
Issue number6
DOIs
StatePublished - Dec 2009

Keywords

  • Angiotensin II
  • Bioactivity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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