EDNO of Venular Origin can Influence Arteriolar Diameter

Abstract

These experiments were designed to test the hypothesis that endothelium-derived nitric oxide (EDNO) produced by a venule can relax arteriolar smooth muscle. To test this hypothesis, large first-order venules were isolated and cannulated in series with arterioles of similar order. The venules contained an intact endothelium whereas arterioles were denuded of endothelium by a physical rubbing technique. Denudation of the arteriole was confirmed by the absence of dilation during exposure to acetylcholine (Ach;10⁻⁶M). The vessels were pressurized to 30 cmH₂O and preconstricted with norepinephrine (Ne; 10⁻¹⁰M). Arteriolar diameter increased as a function of perfusing the venule in the direction of the arteriole with either bradykinin (Bdk; 10⁻⁹M) or Ach (10⁻⁶M). In contrast, reversing the flow (i.e., arteriole to venule) produced a slight degree of arteriolar constriction to each of the agents. The release of venular EDNO was then inhibited with N ^G-monomethyl-Larginine (L-NMMA; 10⁻⁵M; 1 hr) followed by a reassessment of the arteriolar responses to Bdk and Ach. After treatment with L-NMMA the arteriolar dilations previously observed during Ach or Bdk with flow from venule to arteriole were abolished. The collective results of these experiments demonstrate that venular EDNO can relax arteriolar vascular smooth muscle, independent of an intact arteriolar endothelium. Future experiments will address the venular responses to changes in tissue metabolism which may influence the diameter of nearby arterioles via EDNO.