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Research ArticleArticle

Cold Exposure Regulates the Renin-Angiotensin System

Lisa Cassis, Amy Laughter, Mike Fettinger, Scott Akers, Robert Speth, Gerome Burke, Victoria King and Linda Dwoskin
Journal of Pharmacology and Experimental Therapeutics August 1998, 286 (2) 718-726;
Lisa Cassis
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Amy Laughter
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Mike Fettinger
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Scott Akers
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Robert Speth
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Gerome Burke
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Victoria King
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Linda Dwoskin
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Abstract

The effect of cold exposure on the systemic renin-angiotensin system and on regulation of the angiotensin II (Ang II) receptor was examined in target organs for Ang II with cardiovascular relevance (left ventricle, kidney, lung) and metabolic relevance [interscapular brown adipose tissue (ISBAT), liver] to the functional consequences of cold exposure. In time course studies, the effects were examined of 4 hr or 1, 3 and 7 days of exposure to cold (4°C) on plasma Ang II concentration and Ang II receptor binding characteristics in rat liver. Plasma Ang II concentration increased 10-fold after 4 hr of cold exposure, returned to control levels at days 1 and 3 of cold exposure, and was again increased (2-fold) at 7 days of cold exposure. The affinity of [125I]Sar1,Ile8-Ang II binding in membranes prepared from rat liver was not altered in cold-exposed rats. The density (Bmax) of binding sites in liver from cold-exposed rats was increased by day 1 and remained elevated over time-matched controls. Alterations in Ang II receptor density did not parallel plasma Ang II concentration in their time course, suggesting that cold-induced regulation of the Ang II receptor was not substrate mediated. In rats from the 7-day time point of cold exposure, Ang II receptor binding characteristics were examined in ISBAT and lung. Increases in Ang II receptor density were evident in ISBAT but not lung. To determine whether cold-induced increases in food intake contributed to elevations in plasma Ang II concentration and/or Ang II receptor density, a group of cold-exposed rats (7 days) were pair-fed to food intake levels of control rats. Pair-feeding of cold-exposed rats eliminated increases in plasma Ang II and norepinephrine concentration but did not prevent increases in Ang II receptor density in liver, ISBAT, kidney and left ventricle. Moreover, increases in Ang II receptor density were augmented in kidney and left ventricle from cold-exposed rats that were pair-fed. Results from these studies demonstrate that cold exposure resulted in an increase in plasma Ang II concentration through mechanisms related to increased food intake. Elevations in food intake in cold-exposed rats contributed to tissue-specific increases in Ang II receptor density. Moreover, cold-induced increases in Ang II receptor density were not related to plasma Ang II concentration.

Footnotes

  • Send reprint requests to: Lisa A. Cassis, Ph.D., Room 417, College of Pharmacy, Division of Pharmacology and Experimental Therapeutics, University of Kentucky, Lexington, KY 40536-0082.

  • ↵1 This work was supported by the National Heart, Lung and Blood Institute Grant HL52934.

  • Abbreviations:
    NE
    norepinephrine
    Ang II
    angiotensin II
    Ang III
    angiotensin III
    Ang IV
    angiotensin IV
    ISBAT
    interscapular brown adipose tissue
    RIA
    radioimmunoassay
    AT1
    angiotensin type 1 receptor
    HPLC
    high performance liquid chromatography
    BSA
    bovine serum albumin
    EDTA
    ethylenediamine tetraacetic acid
    DMSO
    dimethylsulfoxide
    TFA
    trifluoroacetic acid
    DHBA
    dihydroxybenzylamine
    • Received September 23, 1997.
    • Accepted April 20, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 286, Issue 2
1 Aug 1998
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Research ArticleArticle

Cold Exposure Regulates the Renin-Angiotensin System

Lisa Cassis, Amy Laughter, Mike Fettinger, Scott Akers, Robert Speth, Gerome Burke, Victoria King and Linda Dwoskin
Journal of Pharmacology and Experimental Therapeutics August 1, 1998, 286 (2) 718-726;

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Research ArticleArticle

Cold Exposure Regulates the Renin-Angiotensin System

Lisa Cassis, Amy Laughter, Mike Fettinger, Scott Akers, Robert Speth, Gerome Burke, Victoria King and Linda Dwoskin
Journal of Pharmacology and Experimental Therapeutics August 1, 1998, 286 (2) 718-726;
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