University of Tasmania
Browse

File(s) not publicly available

Vasoconstrictor-mediated increase in muscle resting thermogenesis is inhibited by membrane-stabilizing agents

journal contribution
posted on 2023-05-16, 10:46 authored by Tong, CYA, Stephen RattiganStephen Rattigan, Dora, KA, Michael ClarkMichael Clark
Norepinephrine and angiotensin II are potent vasoconstrictors and stimulate thermogenesis (oxygen uptake) as well as lactate and glycerol efflux in the constant-flow perfused rat hind limb at rest. However, the mechanism by which oxygen uptake (V̇O2) is increased is unknown, and it is not clear whether vasoconstriction is required for the increase in V̇O2 by the hind limb. In the present study the association between vasoconstriction and V̇O2 was further investigated, and a chance observation that high-dose propranolol selectively blocked vasoconstrictor-induced increase in V̇O2 was further explored. The norepinephrine-mediated increase in V̇O2 was totally blocked by either 50 μM (+)-propranolol or 50 μM (-)-propranolol (active β-blocking enantiomer), but only (+)-propranolol reduced the vasoconstriction. Similarly, 100 μM (±)-propranolol (a dose likely to cause plasma membrane stabilizing effects involving interruption and (or) prevention of action potentials) blocked increases in V̇O2, lactate, and glycerol efflux by 5 nM angiotensin II (a nonadrenergic vasoconstrictor) with only marginal effects on pressure development. (±)-Propranolol (100 μM) had no effect on postequilibration red blood cell washout mediated by angiotensin II, a putative indicator of vasoconstrictor-induced redistribution of flow. Quinidine (260 μM) (an antiarrhythmic agent with membrane-stabilizing activity) inhibited only the increase in V̇O2, but neither nadolol (300 μM) nor atenolol (300 μM) (β-blockers without membrane-stabilizing activity) inhibited V̇O2 or perfusion pressure increases produced by 5 nM angiotensin II. Veratridine (a membrane labilizer that is capable of evoking plasma membrane depolarization by maintaining voltage-gated Na+ channels in their open state) increased V̇O2 without vasoconstriction, and the increase in V̇O2 was blocked by 100 μM (±)-propranolol. It is concluded that the increase in hind-limb V̇O2 results from a destabilization of skeletal muscle plasma membranes. This can be achieved directly by veratridine or indirectly by angiotensin II, involving vasoconstriction and redistribution of flow. The findings suggest a novel mechanism for resting muscle thermogenesis.

History

Publication title

Canadian Journal of Physiology and Pharmacology

Volume

75

Issue

7

Pagination

763-771

ISSN

0008-4212

Department/School

Tasmanian School of Medicine

Publisher

National Research Council, Canada

Place of publication

Ottawa, Canada

Repository Status

  • Restricted

Socio-economic Objectives

Expanding knowledge in the environmental sciences

Usage metrics

    University Of Tasmania

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC