The endothelial cell layer releases numerous factors that act on the underlying smooth muscle of arteries to cause relaxation. The relaxation increases arterial diameter and enhances blood flow. Of particular interest to our group are endothelial cell relaxing factors that are produced from the lipid, arachidonic acid. Arachidonic acid is metabolized by endothelial cells to a number of products including epoxy and trihydroxy compounds. These compounds cause relaxation and dilation of arteries by activating specific potassium ion channels on the smooth muscle membrane. Activation of these channels causes potassium ion release from the cell which generates an electrical difference across the smooth muscle membrane. This electrical difference stimulates smooth muscle relaxation and arterial dilation.
Small arteries are especially important in the regulation of tissue blood flow. They are the main sites of blood flow resistance and therefore are the principle regulators of tissue blood perfusion. My research focuses on the effect of arachidonic acid products on smooth muscle relaxation of small resistance arteries. We perform experiments that measure diameters and relaxations of small arteries and we measure potassium channel activity and electrical gradients across the cell membrane to determine the mechanisms of relaxation.
Siangjong L, Gauthier KM, Pfister SL, Smyth EM, Campbell WB. Endothelial 12(S)-HETE vasorelaxation is mediated by thromboxane receptor inhibition in mouse mesenteric arteries. Am J Physiol Heart Circ Physiol. 304:H382-H392, 2012.
Gauthier KM, Olsen L, Harder A, Isbell M, Imig JD, Gutterman DD, Campbell WB. Inhibition of epoxyeicosatrienoic acid vasodilation by catalase: Contamination by soluble epoxide hydrolase. Am J Physiol Renal Physiol. 301:F765-F772, 2011.
Gauthier KM, Goldman DH, Aggarwal NT, Chawengsub Y, Falck JR, Campbell, WB. Role of arachidonic acid lipoxygenase metabolites in acetylcholine relaxations of mouse arteries. Am J Physiol Heart Circ Physiol. 300: H725-H735, 2011.
Gauthier KM, Zhang DX, Cui L, Nithipatikom K, Campbell WB. Angiotensin II relaxations of bovine adrenal cortical arteries: role of angiotensin II metabolites and endothelial NO. Hypertension. 52:150-155, 2008.
Gauthier KM, Chawengsub Y, Goldman D, Conrow RE, Anjaiah S, Falck JR, Campbell WB. 11(R),12(S),15(S)-Trihydroxyeicosa-5(Z),8(Z),13(E)-trienoic acid: an endothelium-derived 15-lipoxygenase metabolite that relaxes rabbit aorta. Am J Physiol Heart Circ Physiol. 294: H1467-H1472, 2008.
Zhang DX, Gauthier KM, Falck JR, Siddam A, Campbell WB. Steroid-producing cells regulate arterial tone of adrenal cortical arteries. Endocrinology. 148:3569-3576, 2007.
Zhang DX, Gauthier KM, Campbell WB. Acetylcholine-induced relaxations of rabbit small mesenteric arteries: role of arachidonic acid metabolites and K+. Am J Physiol Heart Circ Physiol. 293:H152-H159, 2007.
Campbell WB, Holmes BB, Falck JR, Capdevila JH, Gauthier KM. Regulation of potassium channels in coronary smooth muscle by adenoviral expression of cytochrome P450 epoxygenase. Am J Physiol Heart Circ Physiol. 290:H64-H71, 2006.
Gauthier KM, Edwards EM, Falck JR, Reddy DS, Campbell WB. 14,15-Epoxyeicosatrienoic acid represents a transferable endothelium-dependent relaxing factor in bovine coronary arteries. Hypertension. 45:666-671, 2005.
Zhang DX, Gauthier KM, Campbell WB. Acetylcholine-induced relaxation and hyperpolarization in small bovine adrenal arteries: Role of cytochrome P450 metabolites. Endocrinology. 145:4532-4539, 2004.
Gauthier KM, Spitzbarth N, Edwards EM, Campbell WB. Apamin-sensitive K+ currents mediate arachidonic acid-induced relaxations of rabbit aorta. Hypertension. 43:413-419, 2004.
Gauthier KM, Jagadeesh SG, Falck JR, Campbell WB. 14,15-epoxyeicosa-5(Z)-enoic-mSI: a 14,15- and 5,6-EET antagonist in bovine coronary arteries. Hypertension. 42:555-561, 2003.