Abstract
Objective:The growing understanding of the complexity of mechanisms regulating arteriolar tone demands that a systematic determination of how these processes interact to alter diameter be undertaken. This study examined how five mediators of skeletal muscle distal arteriolar tone [adenosine concentration, oxygen content, α-adrenergic activation (norepinephrine), intravascular pressure and wall shear rate], taken two parameters at a time, interact to regulate vessel diameter. Methods:The reactivity of distal arterioles of in siturat cremaster muscle after alterations in each of the above mediators was assessed. In addition, arteriolar responses to all two-parameter combinations were evaluated to determine the effect of altered environment on vascular reactivity to stimuli. Results:Arteriolar dilation to adenosine was unaltered by changes in other parameters. In contrast, wall shear rate-induced arteriolar dilation was impaired by 60–88% after increases in the other parameters. Myogenic reactivity was reduced by 28% with elevated O2and by 65% with norepinephrine (because of vessel closure) and was impaired by 89% with elevated adenosine. O2-induced arteriolar reactivity was impaired by 56% with increased adenosine and by 44% with increased norepinephrine concentration but was largely unaffected by elevated intravascular pressure. Adrenergic reactivity was attenuated with elevated intravascular pressure (by 69%) and O2 (by 54%) because of vessel closure but was unaltered with elevated adenosine. Conclusions:These data suggest that (1) individual mediators contributing to the regulation of arteriolar tone exist within a hierarchy of importance and (2) mechanisms regulating arteriolar tone can be impacted by unidentified alterations in other processes. Ongoing investigation into interactions between multiple processes regulating arteriolar tone will allow for a more integrated understanding of how microvessels regulate their diameter. Microcirculation(2002) 9, 443–462. doi:10.1038/sj.mn.7800160