Cell Biology and Physiology

Nancy L. Kanagy, Ph.D.

Research Interests

My primary research interests are vascular physiology, hypertension and blood pressure control. My current research focuses on altered signal transduction in vascular cells during the development and maintenance of hypertension. This involves studies in vascular smooth muscle cells, endothelial cells and arterial segments. The long-term goal of these investigations is elucidation of the mechanisms responsible for elevated vascular contractility in hypertension and the development of pharmacological tools to reverse this hypersensitivity.

A major emphasis is investigating vascular effects of sleep apnea. We have developed a rat model of sleep apnea by exposing animals to intermittent hypoxia during their sleep period. Using this model, we have determined that the vasoactive peptide endothelin appears to initiate sustained hypertension (Kanagy et al 2001). We have also determined that 14 days of intermittent hypoxia initiates profound vascular changes that alter both endothelial function and vascular smooth muscle cell responses to endothelin. Ongoing studies are investigating the role of reactive oxygen species in these changes and deciphering the molecular mechanisms leading to augmented vasoconstriction to the endogenous peptide, endothelin.

A second ongoing project is investigating the cardiovascular effects of the environmental pollutant, diesel exhaust. We have found that even a short exposure to diesel exhaust causes profound alterations in coronary artery function and that repeated exposures initiate systemic alterations in both cardiac and vascular function.

A final area of research in investigating interactions between the alpha 2 adrenergic receptor and cardiovascular regulation. We have observed that decreased expression of the alpha 2B adrenergic receptor upregulates expression and function of vascular nitric oxide synthase. Ongoing studies are investigating specific molecular targets of this interaction.

Education, Honors and Professional Experience

1980 - 1984, B.A., Chemistry, Goshen College, Goshen, Indiana.
1987 - 1992, Ph.D., Pharmacology, Michigan State University, East Lansing, Michigan.
1992 - 1994, Postdoctoral Fellow, Physiology, University of Michigan, Ann Arbor, Michigan.
1995 - 1997, Assistant Professor of Physiology, University of New Mexico.
1997 - 2001, Assistant Professor of Cell Biology and Physiology, University of New Mexico.
2001 - 2007, Associate Professor of Cell Biology and Physiology, University of New Mexico.
2007 - Present, Professor of Cell Biology and Physiology, University of New Mexico.

Current Lab Personnel

Tom Cherng, Doctoral student
Olan Jackson-Weaver, Doctoral student
Bradley Webster, Doctoral student
Laura Elterman, Undergraduate student
Victoria Youngblood, Undergraduate student
Tamara Berry, Laboratory manager

Selected Recent Publications

KANAGY NL, Walker BR, Nelin LD. Intermittent hypoxia induces endothelin-dependent hypertension. Hypertension 37:511-515, 2001

Thomas C. Resta, Nancy L. KANAGY, and Benjimen R. Walker. Estradiol-induced attenuation of pulmonary hypertension is not associated with altered eNOS expression. American Journal of Physiology. 280: L88-L97, 2001

Mukundan, H., KANAGY, N.L. Altered calcium handling in vascular smooth muscle following nitric oxide synthase inhibition-induced hypertension.American Journal of Physiology, 281:H2233-H2240, 2001

Bratz, I.B., Falcon, R.F., Partridge, L.D., KANAGY, N.L. Vascular smooth muscle cell membrane depolarization following NOS-inhibition hypertension. American Journal of Physiology, 282:H1648-H1655, 2002

Mukundan, H., T.C. Resta and KANAGY, N.L. 17b-estradiol attenuates hypoxic induction of erythropoietin gene expression. American Journal of Physiology, 283:R496-R594, 2002

R.W. Carter and N.L. KANAGY. Tyrosine kinases regulate intracellular calcium during adrenergic receptor contraction in rat aorta. American Journal of Physiology, 283:H1673-H1680, 2002

R.W. Carter, Begaye M and N.L. KANAGY. Acute and chronic NOS inhibition enhances alpha(2)- adrenoreceptor-stimulated RhoA and Rho kinase in rat aorta. American Journal of Physiology, 283:H1361-9, 2002

R.W. Carter and N.L. KANAGY. Role of PKC isoforms in enhanced adrenoreceptor-contraction in NOS inhibition hypertension. Am J Physiol Heart Circ Physiol. 2003 Jan;284(1):H309-16

Lund AK, Goens MB, KANAGY NL, Walker MK. Cardiac hypertrophy in aryl hydrocarbon receptor null mice is correlated with elevated angiotensin II, endothelin and mean arterial blood pressure. Toxicol Appl Pharmacol.2003 Dec 1;193(2)

KANAGY NL, Perrine MF, Cheung DK, Walker BR. Erythropoietin administration in vivo increases vascular nitric oxide synthase expression.JCardiovasc Pharmacol. 2003 Oct;42(4):527

Mukundan H, Resta TC, KANAGY NL. 17 beta estradiol independently regulates erythropoietin synthesis and NOSactivity during hypoxia.JCardiovasc Pharmacol 2004 Feb;43(2):312

Bratz IN, KANAGY NL. Nitric oxide synthase-inhibition hypertension is associated with altered endothelial cyclooxygenase function. Am J Physiol Heart Circ Physiol. 2004 Dec;287(6):H2394-401

Allahdadi KJ, Walker BR, KANAGY NL. Augmented endothelin vasoconstriction in intermittent hypoxia-induced hypertension.Hypertension. 2005 Apr;45(4):705-9.

Bratz IN, Swafford AN Jr, KANAGY NL, Dick GM. Reduced functional expression of K(+) channels in vascular smooth muscle cells from rats made hypertensive with N-ω-nitro-L-arginine. Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1284-90

Bratz IN, Dick GM, Partridge LD, KANAGY NL. Reduced molecular expression of K(+) channel proteins in vascular smooth muscle from rats made hypertensive with N-ω-nitro-L-arginine. Am J Physiol Heart Circ Physiol. 2005 Sep;289(3):H1277-83

KANAGY NL. α2-Adrenergic receptor signalling in hypertension.Clin Sci (Lond). 2005 Nov;109(5):431-7.

Duling LR, Cherng TW, Griego J, Perrine MF, KANAGY NL. Loss of adrenoceptors increases magnitude of NOS-inhibition hypertension. Am J Physiol Heart Circ Physiol. 2006 Nov;291(5):H2403-8.

Allahdadi K, Walker B, KANAGY NL. ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats. Am J Physiol Heart Circ Physiol. 293(5):H291108, 2007.

Silva AQ, Allahdadi KJ, Youngblood VM, KANAGY NL. Reactive Oxygen Species Contribute to Sleep Apnea-induced Hypertension in Rats. (in press) Am J Physiol Heart Circ Physiol. 293(5):H2971-6, 2007.

Allahdadi K, Duling, L.C., Walker B, KANAGY NL. Eucapnic intermittent hypoxia augments endothelin-1 vasoconstriction in rats: role of PKCd. Am J Physiol Heart Circ Physiol. E-published 2008.

Snow J, Kitzis V, Norton C, Torres S, Johnson K, KANAGY NL, Walker BR, and Resta TC. Differential Effects of Chronic and Intermittent Hypoxia on Pulmonary Vasoreactivity. J Applied Physiol 104(1):110-118, 2008.