Hemodynamic consequences of spatially‐dependent sympathetic regulation in skeletal muscle arteriolar trees (678.14)

Abstract

The sympathetic nervous system (SNS) elicits vasoconstriction on skeletal muscle arterioles via release of neurotransmitters norepinephrine (NE; acting on α1‐ and α2R), neuropeptide Y (NPY; acting on Y1R), and adenosine‐triphosphate (ATP; acting on P2X1R). Previous studies have shown that the level of α‐adrenoreceptor modulation is dependent on vessel branch order. However, to date, no studies have investigated the integrated roles of α1R, α2R, Y1R, and P2X1R modulation on arteriolar network hemodynamics. Thus, we evaluated the effects of phenylephrine (PE; α1R agonist), UK 14,304 (UK; α2R agonist), NPY, and ATP on arteriolar diameters in continuously branching arteriolar trees (1st order to 5th order; 1A‐5A). In male rats, concentration‐response curves (PE and ATP: 10‐9‐10‐4M; UK: 10‐9‐10‐5M; NPY: 10‐13‐10‐8M) of arteriolar diameter changes were evaluated in the gluteus maximus muscle (n蠅5 rats/group). Like others, we observed that α1R and α2R control is greatest at large (1A‐2A) arterioles, with declining sensitivity in subsequent branch orders approaching capillaries. Beyond this, we have observed that NPY and ATP elicit the greatest constrictor effects in arterioles closest to capillaries, with declining effects in descending branch orders approaching feed arterioles. Using our theoretical flow model, simulations assessed total flow and red blood cell (RBC) flow heterogeneity within the network using our experimental pharmacological data. Using our experimental inputs, we are the first to illustrate that spatial differences in ligand sensitivity enable the SNS to modify bulk tissue blood flow and RBC distribution differentially in branching networks. Grant Funding Source: NSERC