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.
Recent Publicatons
Falck JR, Krishna UM, Reddy YK, Kumar PS, Reddy KM, Hittner SB, Deeter C, Sharma KK,
Gauthier KM, Campbell WB. Comparison of the vasodilatory properties of 14,15-EET analogs:
structural requirements for dilation. Am J Physiol. 284:H337-H349, 2003.
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(4):555-561, 2003.
Campbell WB, Spitzbarth N, Gauthier KM, Pfister SL. 11,12,15-Trihydroxyeicosatrienoic acid mediates acetylcholine-induced relaxations in the rabbit aorta. Am J Physiol. 285:H2648-H2656, 2003.
Gauthier KM, Falck JR, Campbell WB. 14,15-EET Analogs: characterization of structural requirements for agonists and antagonists activity in bovine coronary arteries. Pharmacological Research. 49:515-524.
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.
Zhang DX, Gauthier KM, Campbell WB. Characterization of vasoconstrictor responses in small bovine adrenal cortical arteries. Endocrinology. 145:1571-1578, 2004.
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, Baewer DV, Hittner S, Hillard CJ, Nithipatikom K, Falck FR, Campbell WB.
Endothelium-derived 2-arachidonylglycerol: An intermediate in vasodilatory eicosanoid release in bovine coronary arteries. In revision, Am J Physiol.
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. Submitted, Hypertension.
Yang W, Reddy LM, Sangras B, Sharma KK, Falck JR, Nithipatikom K, Gauthier KM, Campbell WB. A stable 5,6-EET agonist relaxes coronary arteries through potassium channel activation. Submitted, Hypertension.