Nitric Oxide and Sympatholysis in Rat Soleus Feed Arteries

Abstract

Previous evidence indicates that nitric oxide (NO), acidity, and ATP may all mediate functional sympatholysis. First, we hypothesized that in rat soleus muscle feed arteries, sympatholytic NO is released from vascular endothelial cells by increased shear stress and acts through a guanylyl cyclase intracellular signaling pathway. Second, we hypothesized that NO, acidity and ATP would inhibit sympathetic signaling in a cumulative fashion. Soleus feed arteries (n = 12 per group) were isolated from male Sprague‐Dawley rats and cannulated on two glass micropipettes for in vitro videomicroscopy. We measured the constriction response to the adrenergic agonist phenylephrine (PE; 10−9 M to 10−4 M, 0.5 log increments) in the presence of varying levels of the nitric oxide donor sodium nitroprusside (SNP; 0 nM, 100 nM and 100 mM), shear stress (0 dy/cm2, 25 dy/cm2, and 135 dy/cm2), SNP + ODQ (30 mM), an inhibitor of guanylyl cyclase, and ATP (1 mM and 100 mM) and decreased pH (7.1 and 6.5). SNP reduced constriction to PE in a dose‐dependent manner (maximum constriction 77.3 % vs. 70.7 % and 56.7 %), indicating that NO interferes with sympathetic constriction. ODQ restored PE‐induced constriction (PE alone 77.5%; with SNP 67.6%; with SNP + ODQ 83.5%), indicating that NO causes sympatholysis through a guanylyl cyclase signaling pathway. However, shear stress did not reduce constriction to PE (67.6 % vs. 68.1 %, and 67.6 %), indicating that increased shear stress during exercise is not the source of the NO causing sympatholysis. Finally, SNP alone reduced constriction to PE (maximum constriction 77.3% vs. 70.7% and 56.7%) as much as SNP + low pH (83.5% vs. 71.4% and 59.1%) or SNP + ATP + low pH (75.7% vs. 70.1% and 61.6%), indicating that these sympatholytic agents do not have a cumulative sympatholytic effect. We conclude that nitric oxide acting through guanylyl cyclase causes sympatholysis, but the source of the nitric oxide during exercise is not shear stress‐induced endothelial cell activation.Support or Funding InformationDee Anna Smith Fund for Women in STEM and the Seaver Research Council of Pepperdine University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.