Increased flow precedes remote arteriolar dilations for some microapplied agonists

This study asks which occurs first in time for remote responses: a dilation or a remote change in flow. Arteriolar diameter (~20 pm) and fluorescently labeled red blood cell (RBC) velocity were measured in the cremaster muscle of anesthetized (pentobarbital sodium, 70 mg/kg) hamsters (n = 51). Arterioles were locally stimulated for 60 s with micropipette-applied 10 pg/ml LM-609 (α(v)β₃-integrin agonist), 10^-3 M adenosine, or 10^-3 M 3-morpholinosydnonimine (SIN-1, nitric oxide donor) as remote response agonists or with 10^-3 M papaverine, which dilates only locally. Observations were made at a remote site 1,200 μm upstream. With LM-609 or adenosine, the RBC velocity increased first (within 5 s), and the remote dilation followed 5-7 s later. N-nitro-L-arginine (100 μM) blocked the LM- 609 (100%) and adenosine (60%) remote dilations. SIN-1 induced a concurrent remote dilation and decrease in RBC velocity (~10 s), suggesting the primary signal was to dilate. Papaverine had no remote effects. This study suggests that, although remote responses to some agonists are induced by primary signals to dilate, additionally, network changes in flow can stimulate extensive remote changes in diameter.