Integrated Capillary Responses to Multiple Vasodilators: Implications for Redundancy in Active Hyperaemia

Abstract

There is a distinct lack of evidence that implicates any one vasodilator as necessary in mediating active hyperaemia; we hypothesized this is due to redundant pathways whereby the loss of effects of one dilator can be compensated for by another. For redundancy during hyperaemia, certain dilators released during contraction must alter the vessel's dilatory response to other vasoactive factors. We have shown that redundancy between vasodilators occurs in arterioles whereby potassium (KCl, 10mM) attenuated the magnitude of dilation elicited by nitric oxide (NO) and adenosine (ADO). Given the importance of capillary stimulation in the coordination of blood flow to active skeletal muscle cells we tested capillary responses to ADO and NO in the presence of KCl. Using intravital microscopy of the hamster cremaster, we stimulated capillaries by micropipette application of KCl, ADO or NO and observed the upstream terminal arteriole controlling flow to the stimulated capillary. Separately, 10-6M ADO and 10-6M, S-Nitroso-N-acetylpenicillamine, an NO donor, applied to the capillaries initiated a conducted vasodilation to the upstream terminal arteriole that was significantly attenuated in the presence of 10mM KCl. Further, 10-6M ADO significantly attenuated conducted vasodilation elicited by capillary stimulation with 10mM KCl. These data show capillary responses to vasodilators can be affected by the presence of other vasodilators, providing evidence for redundancy at the level of the capillary. These data imply that redundant mechanisms underlie the hyperaemic response and as the dilatory action of one dilator can be blunted by the presence of another provides a mechanism by which blood flow can be preserved if a vasodilator is suppressed or inhibited. Research funded by NSERC.