{alpha}-Adrenoceptor constrictor responses and their modulation in slow-twitch and fast-twitch mouse skeletal muscle.
Vasoconstrictor responses to sympathetic nerve stimulation and their sensitivity to metabolic modulation reportedly differ in fast-twitch and slow-twitch muscles, but the underlying mechanisms are not known. Both alpha(1)- and alpha(2)-adrenoceptors mediate these vascular responses in fast-twitch muscle, while their roles in slow-twitch muscle are less well defined. In this study, the phosphorylation of smooth muscle myosin regulatory light chain (smRLC) was measured as an index of vasoconstriction in slow-twitch soleus muscles and fast-twitch extensor digitorum longus (EDL) muscles isolated from C57BL/6J mice. In soleus muscles, incubation with phenylephrine (PE) or UK 14,304 to selectively activate alpha(1)- or alpha(2)-adrenoceptors resulted in concentration-dependent increases in smRLC phosphorylation. To evaluate metabolic modulation of these responses, vasodilator pathways previously implicated in such modulation in fast-twitch muscle were activated in soleus muscles by treatment with the nitric oxide (NO) donor nitroprusside or the ATP-sensitive potassium (K(ATP)) channel opener cromakalim. Both drugs inhibited responses to UK 14,304, but not to PE. The effect of nitroprusside to antagonize UK 14,304 responses was prevented by inhibition of guanylyl cyclase or by blockade of K(ATP) channels, but not by blockade of other potassium channels. Results were similar in EDL muscles. These data provide the first evidence for alpha(2)-adrenoceptor-mediated constriction in slow-twitch muscle, and show that it is sensitive to modulation by NO via a cGMP-dependent mechanism that requires K(ATP) channel activation. Based on the similar findings in soleus and EDL muscles, fibre type does not appear to determine the innate vascular response to alpha(1)- or alpha(2)-adrenoceptor activation.
Lambert
David G
DG
Department of Internal Medicine, Hypertension Division, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-8586, USA.
Thomas
Gail D
GD
D000818:Animals; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000502:physiology*; D018656:Muscle Fibers, Fast-Twitch / Q000502:physiology*; D018657:Muscle Fibers, Slow-Twitch / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology*; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha