Vasoconstrictor-mediated increase in muscle resting thermogenesis is inhibited by membrane-stabilizing agents
Tong, CYA and Rattigan, S and Dora, KA and Clark, MG, Vasoconstrictor-mediated increase in muscle resting thermogenesis is inhibited by membrane-stabilizing agents, Canadian Journal of Physiology and Pharmacology, 75, (7) pp. 763-771. ISSN 0008-4212 (1997) [Refereed Article]
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.