Multiple dilator pathways in skeletal muscle contraction-induced arteriolar dilations.

To determine whether nitric oxide (NO), adenosine (Ado) receptors, or ATP-sensitive potassium (K(ATP)) channels play a role in arteriolar dilations induced by muscle contraction, we used a cremaster preparation in anesthetized hamsters in which we stimulated four to five muscle fibers lying perpendicular to a transverse arteriole (maximal diameter approximately 35-65 microm). The diameter of the arteriole at the site of overlap of the stimulated muscle fibers (the local site) and at a remote site approximately 1,000 microm upstream (the upstream site) was measured before, during, and after muscle contraction. Two minutes of 4-Hz muscle stimulation (5-15 V, 0.4 ms) produced local and upstream dilations of 19 +/- 1 and 10 +/- 1 microm, respectively. N(omega)-nitro-L-arginine (10(-4) M; NO synthase inhibitor), xanthine amine congener (XAC; 10(-6) M; Ado A(1), A(2A), and A(2B) receptor antagonist), or glibenclamide (Glib; 10(-5) M; K(ATP) channel inhibitor) superfused over the preparation attenuated the local dilation (by 29.7 +/- 12.7, 61.8 +/- 9.0, and 51.9 +/- 14.9%, respectively), but only XAC and Glib attenuated the upstream dilation (by 68.9 +/- 6.8 and 89.1 +/- 6.4%, respectively). Furthermore, only Glib, when applied to the upstream site directly, attenuated the upstream dilation (48.1 +/- 9.1%). Neither XAC nor Glib applied directly to the arteriole between the local and the upstream sites had an effect on the magnitude of the upstream dilation. We conclude that NO, Ado receptors, and K(ATP) channels are involved in the local dilation initiated by contracting muscle and that both K(ATP) channels and Ado receptor stimulation, but not NO, play a role in the manifestation of the dilation at the upstream site.