Endothelial and Sympathetic Regulation of Vascular Tone in Canine Skeletal Muscle

Abstract

In vitro studies have shown that production of the vasoconstrictor endothelin-1 (ET) is inhibited by NO in porcine aorta (Boulanger & Lüscher, 1990) while in vivo studies have shown that the increase in total peripheral resistance following nitric oxide synthase (NOS) inhibition in anesthetized rats is blunted by blockade of endothelin receptors (Nafrialdi et al., 1994; Richard et al., 1995). In order to assess the role of endothelin in the regulation of resting vascular tone in skeletal muscle, it was first necessary to establish that we could effectively inhibit the vasoconstrictor actions of endothelin in our experimental preparation. Endothelin-1 binds to both ET_A receptors on vascular smooth muscle producing vasoconstriction (Barnes, 1994) and to ET_B receptors on endothelial cells to induce transient vasodilation through stimulation of NO production (Fujitani et al., 1993; Sakurai et al., 1992). The contribution of ET_B receptors in the vasoconstrictor response to ET is minimal, but some studies have demonstrated that the ET_A receptor antagonists BQ123 and FR139317 were unable to fully prevent or reverse the vasoconstrictor effect of endothelin in (Bird & Waldron, 1993; McMurdo et al., 1993). Because the dilatory action of ET is transient, we elected to focus on the vasoconstrictor action of ET.