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Metabolic and vascular actions of endothelin-1 are inhibited by insulin-mediated vasodilation in perfused rat hindlimb muscle

Citation

Kolka, CM and Rattigan, S and Richards, SM and Clark, MG, Metabolic and vascular actions of endothelin-1 are inhibited by insulin-mediated vasodilation in perfused rat hindlimb muscle, British Journal of Pharmacology, 145, (7) pp. 992-1000. ISSN 0007-1188 (2005) [Refereed Article]

Copyright Statement

2005 Nature Publishing Group All rights reserved

DOI: doi:10.1038/sj.bjp.0706263

Abstract

  1. Endothelin-1 (ET-1) is a potent endothelium-derived vasoactive peptide and may be involved in the microvascular actions of insulin for the normal delivery of nutrients to muscle, although higher levels may be antagonistic.
  2. Our aim was to observe the interaction between ET-1 and insulin. Initially, we attempted to distinguish the vascular from the metabolic effects of ET-1 in the constant-flow pump-perfused rat hindlimb by using various doses of ET-1 and measuring changes in perfusion pressure (PP), oxygen consumption (VO2), glucose uptake (GU) and lactate release (LR). Sodium nitroprusside (SNP) was used to block vasoconstriction and to thus assess the relationship between vascular and metabolic effects. Insulin was included in later experiments to determine the interaction between insulin and ET-1 on the above parameters.
  3. ET-1 caused a dose-dependent increase in PP. Effects on VO2 were biphasic, with low doses increasing VO2, and higher doses leading to a net inhibition. GU and LR were increased at lower doses (ET-1 ⩽1 nM), but this effect was lost at higher doses (⩾10 nM ET-1).
  4. SNP (50 μM) fully blocked the increase in pressure and metabolism due to low-dose ET-1 and partly blocked both pressure and metabolic responses by the high dose. ET-1 vasodilatory activity was minimal at high or low dose. Insulin (15 nM) alone caused GU, which was not affected by ET-1. Of the other parameters measured, insulin behaved essentially the same as SNP, inhibiting the pressure and oxygen effects.
  5. Overall, these results show that ET-1 has a biphasic dose-dependent vasoconstrictor effect on hindlimb blood vessels, able to modulate flow to cause both the stimulation and inhibition of metabolism, although these effects are blocked by insulin, which is able to vasodilate against both low and high doses of ET-1.

Item Details

Item Type:Refereed Article
Keywords:endothelin, vasoconstriction, metabolism, blood flow, insulin-mediated glucose uptake
Research Division:Medical and Health Sciences
Research Group:Clinical Sciences
Research Field:Endocrinology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Diabetes
Author:Kolka, CM (Miss Cathryn Kolka)
Author:Rattigan, S (Professor Stephen Rattigan)
Author:Richards, SM (Dr Stephen Richards)
Author:Clark, MG (Professor Michael Clark)
ID Code:37452
Year Published:2005
Web of Science® Times Cited:15
Deposited By:Biochemistry
Deposited On:2005-08-01
Last Modified:2015-09-01
Downloads:0

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