Our laboratory studies the physiology of the cardiovascular system. Of special interest are the effects of impaired oxygenation (hypoxia) on vascular regulation both in the systemic and pulmonary circulations. Within the systemic vasculature, prolonged hypoxia causes diminished reactivity to vasoconstrictor stimuli that persists upon restoration of normal oxygenation. Our recent work suggests that this attenuated reactivity may be the result of enhanced release of the vasodilators carbon monoxide and epoxyeicosatrienoic acids (EETs) from the vascular endothelium. Current experiments are examining the possible role of endothelial large conductance calcium-activated potassium channels (BK) as targets for these vasodilators. Another result of chronic hypoxia is the development of pulmonary hypertension. We have recently shown that endothelial cell calcium entry is impaired in this setting which may have significant effects on vascular control. We are currently examining the mechanism for this derangement. A number of approaches are employed in our laboratory to study vasoreactivity, including the study of conscious, chronically instrumented animals, isolated organs and pressurized resistance vessels. We also are able to perform intracellular calcium imaging and electrophysiological measurements in addition to molecular biological approaches to assess the functional consequences of altered gene expression within the vasculature. This integrated approach allows us to investigate how altered vascular gene expression affects the physiological responses of the whole animal as well as to determine the cellular mechanisms that may be altered by stimuli such as hypoxia.
B.S., Biology, Southern Colorado State College
M.S., Zoology and Physiology, University of Wyoming
Ph.D., Physiology, State University of New York at Buffalo School of Medicine
Postdoctoral Fellow, University of Colorado Health Sciences Center
Assistant Professor of Physiology, Tulane University School of Medicine
Associate Professor of Physiology, Tulane University School of Medicine
Assistant Professor of Physiology, University of New Mexico School of Medicine
Associate Professor of Physiology, UNMSOM
Professor of Cell Biology and Physiology, UNMSOM, 1995 – present
Established Investigator of the American Heart Association
UNMSOM Faculty Teaching Excellence Award, 1998-99, 2000-01
William G. Dail Award, 2008
Fellow, Cardiovascular Section of American Physiological Society
Minerva Murphy, B.S., Senior Research Technician
Melissa Riddle, Graduate Student
Selected Recent Publications (click on reference for PubMed abstract)
Cherng, T.W., M.L. Paffett, O. Jackson-Weaver, M.J. Campen, B.R. Walker, and N.L. Kanagy. Mechanisms of diesel-induced endothelial nitric oxide synthase dysfunction in coronary arterioles. Environ. HealthPerspect. In Press.
Hughes, J.M., M.A. Riddle, M.L. Paffett, L.V. Gonzalez Bosc and B.R. Walker. Novel role of endothelial BKCa channels in altered vasoreactivityfollowing chronic hypoxia. Am. J. Physiol. In Press.
Paffett, M.L., M.A. Riddle, N.L. Kanagy, T.C. Resta and B.R. Walker. Altered PKC regulation of pulmonary endothelial store- and receptor-mediated Ca2+ entry following chronic hypoxia. J. Pharmacol. Exp. Ther. 334: 753-760, 2010.
Gonzalez Bosc, L.V., T. Resta, B. Walker and N.L. Kanagy. Mechanisms of intermittent hypoxia-induced hypertension. J. Cell. Mol. Med. 14: 3-17, 2010.
Sweazea, K.L., N.L. Kanagy and B.R. Walker. Increased adiposity does not exacerbate impaired vasodilation in rats exposed to eucapnicintermittent hypoxia. Respiration In Press.
Sweazea, K.L., M. Lekic and B.R. Walker. Comparison of mechanisms involved in impaired vascular reactivity between high sucrose and high fat diets in rats. Nutrition and Metabolism 7: 48 (1-10), 2010. PMCID: PMC2887873
Jernigan, N.L., M.L. Paffett, B.R. Walker and T.C. Resta. ASIC1 contributes to pulmonary vascular smooth muscle store-operated Ca2+entry. Am. J. Physiol. 297: L271-L285, 2009. PMCID: PMC2742795
Sweazea, K.L. and B.R. Walker. Antioxidant and vasodilatory effects of heme oxygenase on mesenteric vasoreactivity following chronic hypoxia.
Microcirculation 16: 131-141, 2009.
Chang, R., L.G. Chicoine, H. Cui, N.L. Kanagy, B.R. Walker,Y. Liu, B.K. English and L.D. Nelin. Cytokine-induced arginase activity in pulmonary endothelial cells depends on src-family tyrosine kinase activity.
Am. J. Physiol. 295: L688-L697, 2008.
Snow, J.B., Kitsis, V., C.E. Norton, S.N. Torres, K.D. Johnson, N.L. Kanagy, B.R. Walkerand T.C. Resta. Differential effects of chronic and intermittent hypoxia on pulmonary vasoreactivity.
J. Appl. Physiol. 104: 110-118, 2008.
Allahdadi, K.J., L.C. Duling, B.R. Walker and N.L. Kanagy. Eucapnic intermittent hypoxia augments endothelin-1 constriction: role of PKCd.
Am. J. Physiol. 294: H920-H927, 2008.
Broughton, B.R.S., B.R. Walker and T.C. Resta. Chronic hypoxia induces Rho kinase-dependent myogenic tone in small pulmonary arteries.
Am. J. Physiol. 294: L797-L806, 2008.
Gonzales, R.J., J.M. Bryant, J.S. Naik, T.C. Resta and B.R. Walker. Gender differences in mesenteric vasoconstrictor reactivity following chronic hypoxia.
Microcirculation 15: 473-484, 2008.
Allahdadi, K.J., T.H. Cherng, H. Pai, A.Q. Gomez da Silva, B.R. Walker, L.D. Nelin and N.L. Kanagy. Endothelin A receptor antagonism reverses intermittent hypoxia-induced hypertension.
Am. J. Physiol. 295: H434-H440, 2008.
Jernigan, N.L., B.R. Walker and T.C. Resta. Reactive oxygen species mediate rhoA/rho kinase-induced Ca2+ sensitization in pulmonary vascular smooth muscle following chronic hypoxia.
Am. J. Physiol. 295: L515-L529, 2008.
Chicoine, L.G., M.L. Paffett, M.R. Girton, M. Metroupolus, M.S. Joshi, J.A. Bauer, L.D. Nelin, T.C. Resta and B.R. Walker. Maturational changes in the regulation of pulmonary vascular tone by nitric oxide in neonatal rats. Am. J. Physiol. 293: L1261-L1270, 2007.
Paffett, M.L. and B.R. Walker. Vascular adaptations to hypoxia: molecular and cellular mechanisms regulating vascular tone.
Essays in Biochem. 43: 105-120, 2007.
Allahdadi, K.J., B.R. Walker and N.L. Kanagy. ROK contribution to endothelin-1-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia.
Am. J. Physiol. 293: H2911-H2918, 2007.
Paffett, M.L., J.S. Naik, T.C. Resta and B.R. Walker. Reduced store-operated calcium entry in pulmonary endothelial cells from chronically hypoxic rats.
Am. J. Physiol. 293: L1135-L1142, 2007.
Naik, J.S. and B.R. Walker. Role of vascular heme oxygenase in reduced myogenic reactivity following chronic hypoxia.
Microcirculation 13: 81-88, 2006.
Jernigan, N.L., B.R.S. Broughton, B.R. Walker and T.C. Resta. Impaired NO-dependent inhibition of store- and receptor-operated calcium entry in pulmonary vascular smooth muscle following chronic hypoxia.
Am. J. Physiol. 290: L517-L525, 2006.
Allahdadi, K., B.R. Walker and N.L. Kanagy. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension.
Hypertension 45: 705-709, 2005.
Naik, J.S., S. Earley, T.C. Resta and B.R. Walker. Pressure-induced smooth muscle depolarization in pulmonary arteries from control and chronically hypoxic rats does not cause myogenic vasoconstriction. J.
Appl. Physiol. 98: 1119-1124, 2005.
Earley, S., T.C. Resta and B.R. Walker. Disruption of smooth muscle gap junctions attenuates myogenic vasoconstriction of mesenteric resistance arteries.
Am. J. Physiol.: Heart and Circ. Physiol. 287: H2677-H2686, 2004.
Jernigan, N.L., B.R. Walker and T.C. Resta. Chronic hypoxia augments protein kinase G-mediated Ca2+ desensitization in pulmonary vascular smooth muscle through inhibition of RhoA/Rho kinase signaling.
Am. J. Physiol.: Lung Cell. Mol. Physiol. 287: L1220-L1229, 2004.
Chicoine, L.G., E. Tzeng, R. Bryan, S. Saenz, M.L. Paffett, J. Jones, C.R. Lyons, T.C. Resta, L.D. Nelin and B.R. Walker. Intratracheal adenoviral iNOS transduction decreases pulmonary vasoconstrictor responses in rats.
J. Appl. Physiol. 97: 1814-1822, 2004.
Jernigan, N.L., B.R. Walker and T.C. Resta. Endothelium-derived reactive oxygen species and endothelin-1 attenuate NO-dependent pulmonary vasodilation following chronic hypoxia.
Am. J. Physiol.: Lung Cell. Mol. Physiol. 287: L801-L808, 2004.
Jernigan, N.L., T.C. Resta and B.R. Walker. Contribution of oxygen radicals to altered NO-dependent pulmonary vasodilation in acute and chronic hypoxia.
Am. J. Physiol.: Lung, Cell. Mol Physiol. 286: L947-L955, 2004.