High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle

Paul J. Marvar, J R Falck, Matthew A. Boegehold

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The coupling of tissue blood flow to cellular metabolic demand involves oxygen-dependent adjustments in arteriolar tone, and arteriolar responses to oxygen can be mediated, in part, by changes in local production of 20-HETE. In this study, we examined the long-term effect of dietary salt on arteriolar oxygen responsiveness in the exteriorized, superfused rat spinotrapezius muscle and the role of 20-HETE in this responsiveness. Rats were fed either a normal-salt (NS, 0.45%) or high-salt (HS, 4%) diet for 4-5 wk. There was no difference in steady-state tissue PO2 between NS and HS rats, and elevation of superfusate oxygen content from 0% to 10% caused tissue PO 2 to increase by the same amount in both groups. However, the resulting reductions in arteriolar diameter and blood flow were less in HS rats than NS rats. Inhibition of 20-HETE formation with N-methylsulfonyl-12,12- dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA) attenuated oxygen-induced constriction in NS rats but not HS rats. Exogenous 20-HETE elicited arteriolar constriction that was greatly reduced by the large-conductance Ca2+-activated potassium (KCa) channel inhibitors tetraethylammonium chloride (TEA) and iberiotoxin (IbTx) in NS rats and a smaller constriction that was less sensitive to TEA or IbTx in HS rats. Arteriolar responses to exogenous angiotensin II were similar in both groups but more sensitive to inhibition with DDMS in NS rats. Norepinephrine-induced arteriolar constriction was similar and insensitive to DDMS in both groups. We conclude that 20-HETE contributes to oxygen-induced constriction of skeletal muscle arterioles via inhibition of KCa channels and that a high-salt diet impairs arteriolar responses to increased oxygen availability due to a reduction in vascular smooth muscle responsiveness to 20-HETE.

Original languageEnglish (US)
Pages (from-to)H1507-H1515
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • 20-hydroxyeicosatetraenoic acid
  • Blood flow
  • NaCl
  • Vascular control

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle'. Together they form a unique fingerprint.

  • Cite this