Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors

Cuihua Zhang, Jarrod D. Knudson, Srinath Setty, Alberto Araiza, Ü Deniz Dincer, Lih Kuo, Johnathan Tune

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

The metabolic syndrome is associated with activation of the renin-angiotensin system. However, whether the coronary vascular response to ANG II is altered under this condition is unknown. Experiments were conducted in control and chronically high-fat-fed dogs with the prediabetic metabolic syndrome both in vitro (isolated coronary arterioles, 60-110 μm) and in vivo (anesthetized and conscious). We found that plasma renin activity and ANG II levels are elevated in high-fat-fed dogs and that this increase in ANG II is associated with a significant increase in ANG II-mediated coronary vasoconstriction in isolated coronary arterioles and in anesthetized open-chest dogs. The vasoconstriction to ANG II is abolished by ANG II type 1 (AT 1) receptor blockade. In conscious chronically instrumented dogs, AT1 receptor blockade with telmisartan improved the balance between coronary blood flow and myocardial oxygen consumption in the high-fat-fed dogs but not in normal control dogs, i.e., the relationship between coronary venous PO2 and myocardial oxygen consumption was shifted upward, toward normal control values. Quantitative assessment of coronary arteriolar AT 1 and ANG II type 2 (AT2) receptor mRNA levels by real-time PCR revealed no significant difference between normal control and high-fat-fed dogs; however, Western blot analysis showed a significant increase in AT1 receptor protein level with no change in AT2 receptor protein density. These findings indicate that AT1 receptor-mediated coronary constriction is augmented in the prediabetic metabolic syndrome and contributes to impaired control of coronary blood flow via increases in circulating ANG II and/or coronary arteriolar AT1 receptor density.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume288
Issue number5 57-5
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Vasoconstriction
Angiotensin II
Dogs
Fats
Arterioles
Oxygen Consumption
Renin-Angiotensin System
Renin
Constriction
Blood Vessels
Real-Time Polymerase Chain Reaction
Reference Values
Proteins
Thorax
Western Blotting
Messenger RNA

Keywords

  • Blood flow
  • Exercise
  • Microcirculation
  • Obesity

ASJC Scopus subject areas

  • Physiology

Cite this

Coronary arteriolar vasoconstriction to angiotensin II is augmented in prediabetic metabolic syndrome via activation of AT1 receptors. / Zhang, Cuihua; Knudson, Jarrod D.; Setty, Srinath; Araiza, Alberto; Dincer, Ü Deniz; Kuo, Lih; Tune, Johnathan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 288, No. 5 57-5, 05.2005.

Research output: Contribution to journalArticle

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