Universidad Nacional de La Plata, Argentina, 1962 3017 Wahl Hall East
3901 Rainbow Boulevard
Kansas City, KS66160-7401
Phone: (913) 588-7028
Fax: (913) 588-7430
ngonzale@kumc.edu
My research centers on the mechanisms of adaptation of intact organisms to environmental hypoxia. Environmental hypoxia typically occurs during exposure to altitude and results in alterations in systemic O2 transport and limitations in exercise capacity. Individual that ascend to altitude rapidly may develop acute altitude illnesses such as acute mountain sickness, high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE). Acclimatized individuals, or persons indigenous to high altitude may develop chronic mountain sickness, or Monge’s disease, which is characterized by excessive polycythemia.
My laboratory has been involved in studies directed to determine the mechanisms for the limitations in systemic O2 transport during maximal exercise in acute and chronic hypoxia, using a model which allowed the characterization of the various steps in systemic O2 transport from the environment to the tissue capillary.
A second line of research is the role of inflammation in the pathophysiology of acute illnesses of altitude. Recent studies in collaboration with Dr. John Wood have shown that rats and mice exposed to hypoxia develop a rapid and ubiquitous inflammatory response characterized by increased ROS and reduced NO levels in various microcirculatory beds, activations of perivascular mast cells, leukocyte recruitment and increased vascular permeability. If the animals are maintained in hypoxia for 2-3 weeks, the inflammation disappears and the animals do not demonstrate increased in inflammatory markers if exposed to even more severe hypoxia.
Characteristics of hypoxia-induced inflammation
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Current efforts are directed to test the hypothesis that the systemic inflammation of hypoxia Is triggered by an agent released from a distant site and transported by the circulation. This agent would initiate the inflammation by sctivating perivascular mast cells.
Representative publications
N.C. Gonzalez, R.L. Clancy and P.D. Wagner. Determinants of maximum oxygen uptake in rats acclimated to simulated altitude. J. Appl. Physiol. 75:1608-1614, 1993.
N.C. Gonzalez, K. Perry, Y. Moue, R.L. Clancy and J. Piiper. Pulmonary gas exchange during hypoxic exercise in the rat. Respir. Physiol.96: 111-125, 1994.
N.C. Gonzalez, L.P. Erwig, C.F. Painter, R.L. Clancy and P.D. Wagner. Effect of hematocrit on systemic O2 transport in hypoxic and normoxic exercise in rats. J.Appl.Physiol. 77:1341-1348, 1994
Y. Moue, P.G. Smith, R.L. Clancy and N.C. Gonzalez. Role of vasoconstrictors in the systemic hypertension of rats acclimatized to hypoxia. J.Appl.Physiol. 79: 1657-1667, 1995
I. Kuwahira, Y. Moue, Y. Ohta and N.C. Gonzalez. Chronic hypoxia decreases heterogeneity of pulmonary blood flow distribution in rats. Respir. Physiol. 104:205-212, 1996
R.L. Clancy, Y. Moue, L.P. Erwig, P.G. Smith and N.C. Gonzalez. Role of ß-adrenergic and cholinergic systems in acclimatization to hypoxia in rats. Respir Physiol. 107:75-84, 1997
N.C. Gonzalez, R.L. Clancy, Y. Moue and J.P. Richalet. Increasing maximal heart rate increases maximal oxygen uptake in rats acclimatized to simulated altitude J.Appl.Physiol. 84:164-168, 1998
W. McCanse, K.Henderson, T.Urano, I, Kuwahira, R.L. Clancy and N.C. Gonzalez. Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise. J.Appl.Physiol. 86:1257-1263, 1999
Wood, L.F. Mattioli and N.C. Gonzalez. Hypoxia causes leukocyte adherence to mesenteric venules in non-acclimatized rats but not after acclimatization. J.Appl.Physiol. 86:873-881, 1999.
J.G. Wood, J.S. Johnson, L.F. Mattioli and N.C. Gonzalez. Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation. J.Appl.Physiol 87:1734-1740, 1999
K.K. Henderson, W.McCanse, T.Urano, I. Kuwahira, R.L.Clancy and N.C. Gonzalez. Acute vs. chronic effects of elevated hemoglobin O2 affinity on O2 transport in maximal exercise. J.Appl.Physiol. 89:265-272, 2000
J.G.Wood, J.S.Johnson, L.F. Mattioli and N.C. Gonzalez. Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats. J.Appl.Physiol. 89:1561-1568, 2000
F.Favret, J.P. Richalet, K.K. Henderson, R. Germack and N.C. Gonzalez. Myocardial adrenergic and cholinergic receptor function in hypoxia: correlation with systemic O2 transport in exercise. Amer. J. Physiol: Regulatory Integrative Comp Physiol, 280:R730-R738, 2001
I.Kuwahira, Y. Moue, U. Kamiya, T. Iwamoto, M. Ishii, R.L. Clancy and N.C. Gonzalez. Redistribution of pulmonary blood flow during hypoxic exercise. Int J Sports Med 22:1-7, 2001
K.K. Henderson, R.L. Clancy and N.C. Gonzalez. Living and training in moderate hypoxia increases VO2max as much as living and training in normoxia. J.Appl. Physiol: 90:2057-2062, 2001
K.K. Henderson, H. Wagner, F. Favret, S.L. Britton, L.G. Koch, P.D. Wagner and N.C. Gonzalez. Determinants of maximal O2 uptake in rats selectively bred for exercise endurance. J Appl Physiol 93: 1265-1274, 2002
D.R. Steiner, N.C. Gonzalez and J.G. Wood. Interactions between reactive oxygen species and nitric oxide in the microvascular response to hypoxia. J. Appl Physiol. 93:1411-1418, 2002
D.R.S. Steiner, N.C. Gonzalez and J.G.Wood. Mast cells mediate the microvascular inflammatory response to hypoxia. J Appl Physiol 94: 325-334, 2003.
R.A. Howlett, N.C. Gonzalez, H.E. Wagner, Z. Fu, S.L. Britton, L.G. Koch and P.D. Wagner. Skeletal muscle capillarity and enzyme activity in rats selectively bred for running endurance. J Appl Physiol 94:1682-1688, 2003 .
A.J Casillan, N.C Gonzalez, J.S. Johnson, D.R.S. Steiner and J.G. Wood. Mesenteric inflammatory microvascular responses to systemic hypoxia are mediated by PAF and LTB4. J Appl Physiol, 94: 2313-2322, 2003
S, Shah J. Allen, J.G. Wood and N.C. Gonzalez. Dissociation between microvascular PO2 and hypoxia-induced microvascular inflammation. J Appl Physiol 94:2323-2329, 2003
F. Favret K.K Henderson, J.P. Richalet and N.C. Gonzalez. Effects of exercise training on acclimatization to hypoxia: systemic O2 transport during maximal exercise. J.Appl Physiol 95:1531-1541, 2003
R.Dix, T.Orth, J. Allen, J.G. Wood and N.C. Gonzalez. Activation of mast cells by systemic hypoxia, but not by local hypoxia, mediates increased leukocyte-endothelial adherence in cremaster venules. J Appl Physiol 95: 2495-2502, 2003
T Orth, J Allen, JG Wood and NC Gonzalez. Exercise training prevents the inflammatory response to hypoxia in cremaster venules. J Appl Physiol 98: 2113-2118, 2005
T Orth, J Allen, JF Wood and NC Gonzalez. Plasma from conscious hypoxic rats stimulates leukocyte-endothelial interactions in normoxic cremaster venules. J Appl Physiol 99:290-297, 2005
F Favret, KK Henderson, J Allen, JP Richalet and NC Gonzalez. Exercise training improves pulmonary gas exchange and attenuates hypoxic pulmonary vasoconstriction, but does not alter chronic hypoxic pulmonary hypertension. J Appl Physiol 100: 20-25, 2006
NC Gonzalez, R. Howlett, S. Kirkton Dritton, S, Koch L, Wagner H and Wagner PD. Continued divergence in VO2max of rats artificially selected for running endurance is mediated by greater convective blood O2 delivery. J Appl Physiol101(5):1288-96. 2006
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