Neurohumoral control of veins in hypertension

Summary

Principal Investigator: Gregory D Fink
Abstract: DESCRIPTION (provided by applicant): Hypertension is a significant public health concern around the world because it is an important risk factor for cardiovascular and renal disease. Most efforts to understand and treat this condition have focused logically on either the kidney or arteries. The three central and complementary themes of this Program Project are: veins play an important role in the long-term control of arterial pressure;neurohumoral mechanisms regulating venous smooth muscle activity are fundamentally different from those of arteries;and abnormalities in neurohumoral regulation specific to veins are a significant part of the etiology of hypertension. The overall strategy for achieving the experimental goals listed above will be to capitalize on the diverse scientific expertise of individual project investigators - from whole animal studies to molecular approaches - to test in detail a single integrated hypothesis linking the sympathetic nervous system, ET-1 and reactive oxygen species to the control of venomotor tone and blood pressure. We will focus our efforts on understanding the etiology of hypertension primarily using the DOCA-salt model of hypertension in rats. Project 1 will assess venous function in conscious rats using a number of whole body measures including blood pressure, mean circulatory filling pressure, cardiac output, and fluid volume distribution using bioimpedance. Project 2 focuses on differences in adrenergic neurotransmission in veins versus arteries and the adaptive mechanisms of veins to hypertension. Project 3 aims at comparing properties of sympathetic neurons targeting arteries, veins and the heart in normotensive and hypertensive rats, and the generation and effects of superoxide and other reactive oxygen species in sympathetic ganglia. Project 4 will investigate arterial vs venous function by examining how ET receptors operate differently in arteries versus veins, why arteries and veins have different reactive oxygen species metabolizing systems and why veins and arteries have a different response (adaptive or otherwise) to the stresses of hypertension. Lay Summary: High blood pressure (hypertension) is a major human health problem. Many scientists feel the causes of hypertension can be found in abnormal function of the kidney or arteries. This project tests the idea that altered structure or function of veins also may cause hypertension, and that it may be possible to treat hypertension using drugs that affect veins.
Funding Period: 2002-07-01 - 2015-01-31
more information: NIH RePORT

Top Publications

  1. pmc Large-conductance Ca2+-activated K+ channel beta1-subunit knockout mice are not hypertensive
    Hui Xu
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
    Am J Physiol Heart Circ Physiol 300:H476-85. 2011
  2. pmc Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model
    Theodora Szasz
    Pharmacology and Toxicology Department, Michigan State University, East Lansing, MI 48824 1317, USA
    J Cardiovasc Pharmacol 56:627-34. 2010
  3. pmc The interdependence of endothelin-1 and calcium: a review
    Nathan R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Clin Sci (Lond) 119:361-72. 2010
  4. pmc Interaction between alpha(1)- and alpha(2)-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries
    Alexandra Sporkova
    Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Eur J Pharmacol 643:239-46. 2010
  5. pmc Antioxidant treatment restores prejunctional regulation of purinergic transmission in mesenteric arteries of deoxycorticosterone acetate-salt hypertensive rats
    S L Demel
    The Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    Neuroscience 168:335-45. 2010
  6. pmc P2Y2 receptors mediate ATP-induced resensitization of TRPV1 expressed by kidney projecting sensory neurons
    Hui Wang
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Am J Physiol Regul Integr Comp Physiol 298:R1634-41. 2010
  7. pmc Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats
    Theodora Szasz
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824 1317, USA
    J Pharmacol Exp Ther 333:758-63. 2010
  8. ncbi The effects of celiac ganglionectomy on sympathetic innervation to the splanchnic organs in the rat
    Melissa Li
    Department of Pharmacology and Toxicology, B440 Life Sciences, Michigan State University, East Lansing, MI 48824, USA
    Auton Neurosci 154:66-73. 2010
  9. pmc Endothelin receptors: what's new and what do we need to know?
    Stephanie W Watts
    Dept of Pharmacology and Toxicology, B445 Life Sciences Bldg, East Lansing, MI 48824 1317, USA
    Am J Physiol Regul Integr Comp Physiol 298:R254-60. 2010
  10. ncbi Could hypertension possibly be adaptive?
    E S Prakash
    Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia
    Clin Exp Pharmacol Physiol 37:e99-e106. 2010

Research Grants

  1. The Center for Native and Pacific Health Disparities Research
    MARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013
  2. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
  3. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
  4. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
  5. AMPK Endothelial Cell Dysfunction and the Metabolic Syndrome (PROGRAM PROJECT)
    Neil B Ruderman; Fiscal Year: 2013
  6. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013

Detail Information

Publications55

  1. pmc Large-conductance Ca2+-activated K+ channel beta1-subunit knockout mice are not hypertensive
    Hui Xu
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
    Am J Physiol Heart Circ Physiol 300:H476-85. 2011
    ..BK and L-type Ca(2+) channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension...
  2. pmc Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model
    Theodora Szasz
    Pharmacology and Toxicology Department, Michigan State University, East Lansing, MI 48824 1317, USA
    J Cardiovasc Pharmacol 56:627-34. 2010
    ..We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model...
  3. pmc The interdependence of endothelin-1 and calcium: a review
    Nathan R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Clin Sci (Lond) 119:361-72. 2010
    ..A list of unanswered questions regarding ET-mediated calcium signals are also presented, as well as perspectives for future research of calcium mobilization by ET-1...
  4. pmc Interaction between alpha(1)- and alpha(2)-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries
    Alexandra Sporkova
    Institute for Clinical and Experimental Medicine, Prague, Czech Republic
    Eur J Pharmacol 643:239-46. 2010
    ..This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific alpha(2)-adrenoceptor linked Ca(2+) and perhaps other signaling pathways account for enhanced venous adrenergic reactivity...
  5. pmc Antioxidant treatment restores prejunctional regulation of purinergic transmission in mesenteric arteries of deoxycorticosterone acetate-salt hypertensive rats
    S L Demel
    The Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    Neuroscience 168:335-45. 2010
    ..Regulation of norepinephrine release by alpha(2)-autoreceptors and P/Q-type channels is impaired in DOCA-salt hypertension and alpha(2)-autoreceptor function is disrupted by oxidative stress...
  6. pmc P2Y2 receptors mediate ATP-induced resensitization of TRPV1 expressed by kidney projecting sensory neurons
    Hui Wang
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Am J Physiol Regul Integr Comp Physiol 298:R1634-41. 2010
    ..We conclude that P2Y(2) receptor activation can maintain TRPV1 function perhaps during sustained episodes of activity of kidney projecting sensory neurons...
  7. pmc Uric acid does not affect the acetylcholine-induced relaxation of aorta from normotensive and deoxycorticosterone acetate-salt hypertensive rats
    Theodora Szasz
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824 1317, USA
    J Pharmacol Exp Ther 333:758-63. 2010
    ..We conclude that, at least in vitro, UA does not affect the ACh-induced relaxation of normotensive and DOCA-salt hypertensive rats...
  8. ncbi The effects of celiac ganglionectomy on sympathetic innervation to the splanchnic organs in the rat
    Melissa Li
    Department of Pharmacology and Toxicology, B440 Life Sciences, Michigan State University, East Lansing, MI 48824, USA
    Auton Neurosci 154:66-73. 2010
    ..Therefore, CGX is an effective means to impair sympathetic input to the splanchnic organs, but the effect of the procedure is not permanent...
  9. pmc Endothelin receptors: what's new and what do we need to know?
    Stephanie W Watts
    Dept of Pharmacology and Toxicology, B445 Life Sciences Bldg, East Lansing, MI 48824 1317, USA
    Am J Physiol Regul Integr Comp Physiol 298:R254-60. 2010
    ..Do these exist for ET receptors and can we take advantage of this possibility in drug design? These and other questions will be posed in this minireview on topics on ET receptors...
  10. ncbi Could hypertension possibly be adaptive?
    E S Prakash
    Faculty of Medicine, AIMST University, Bedong, Kedah, Malaysia
    Clin Exp Pharmacol Physiol 37:e99-e106. 2010
    ..4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested...
  11. pmc Mild DOCA-salt hypertension: sympathetic system and role of renal nerves
    Sachin S Kandlikar
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA
    Am J Physiol Heart Circ Physiol 300:H1781-7. 2011
    ..In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model...
  12. pmc Heterogeneous function of ryanodine receptors, but not IP3 receptors, in hamster cremaster muscle feed arteries and arterioles
    Erika B Westcott
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA
    Am J Physiol Heart Circ Physiol 300:H1616-30. 2011
    ....
  13. pmc Indoleamine 2,3-diooxygenase in periaortic fat: mechanisms of inhibition of contraction
    Stephanie W Watts
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan 48824 1317, USA
    Am J Physiol Heart Circ Physiol 301:H1236-47. 2011
    ..We conclude that IDO is an enzyme active primarily in brown fat surrounding the thoracic aorta and depresses aortic contractility...
  14. pmc Divergent signaling mechanisms for venous versus arterial contraction as revealed by endothelin-1
    Nathan R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Mich Electronic address
    J Vasc Surg . 2014
    ..This produces two functional arms of signaling: diacylglycerol (DAG; protein kinase C [PKC] activation) and inositol trisphosphate (IP3) production (intracellular calcium release)...
  15. pmc Regional changes in cardiac and stellate ganglion norepinephrine transporter in DOCA-salt hypertension
    Erica A Wehrwein
    Department of Physiology, Michigan State University, East Lansing, MI, United States Electronic address
    Auton Neurosci 179:99-107. 2013
    ....
  16. pmc Chemerin connects fat to arterial contraction
    Stephanie W Watts
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Arterioscler Thromb Vasc Biol 33:1320-8. 2013
    ..We presently tested the hypothesis that chemerin is expressed in perivascular adipose tissue and is vasoactive, supporting the existence of a chemerin axis in the vasculature...
  17. pmc Impaired function of prejunctional adenosine A1 receptors expressed by perivascular sympathetic nerves in DOCA-salt hypertensive rats
    Sutheera Sangsiri
    Departments of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA
    J Pharmacol Exp Ther 345:32-40. 2013
    ..Sympathetic autoreceptor dysfunction is not specific to α2ARs, but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA-salt hypertension...
  18. pmc Ryanodine receptors are uncoupled from contraction in rat vena cava
    N R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue St Room B 445, East Lansing, MI 48824, USA
    Cell Calcium 53:112-9. 2013
    ..These data suggest that ryanodine receptors, while present in both RA and RVC, are inactive and uncoupled from Ca(2+) release and contraction in RVC...
  19. pmc Reverse-mode Na+/Ca2+ exchange is an important mediator of venous contraction
    Nathan R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, 1355 Bogue St Rooms B 420 and B 445, East Lansing, MI 48824, USA
    Pharmacol Res 66:544-54. 2012
    ..Also, the effects of KB-R7943 on ET-1-induced contraction of RA and RVC are predominantly mediated by reverse-mode NCX inhibition and not due to off-target inhibition of Ca(2+) channels...
  20. pmc Function and expression of ryanodine receptors and inositol 1,4,5-trisphosphate receptors in smooth muscle cells of murine feed arteries and arterioles
    Erika B Westcott
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    J Physiol 590:1849-69. 2012
    ..We conclude that vasomotor control is differentially regulated in feed arteries vs. downstream arterioles...
  21. pmc Vena cava and aortic smooth muscle cells express transglutaminases 1 and 4 in addition to transglutaminase 2
    Kyle B Johnson
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, 48824, USA
    Am J Physiol Heart Circ Physiol 302:H1355-66. 2012
    ..These studies demonstrate that TG2-independent TG activity exists in the vasculature and that TG1 and TG4 are expressed in vascular tissues...
  22. pmc Splanchnic sympathetic nerves in the development of mild DOCA-salt hypertension
    Sachin S Kandlikar
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Am J Physiol Heart Circ Physiol 301:H1965-73. 2011
    ..Increased splanchnic vascular reactivity to NE during DOCA-salt treatment is one possible explanation...
  23. pmc Requirement for functional BK channels in maintaining oscillation in venomotor tone revealed by species differences in expression of the β1 accessory subunits
    Hui Xu
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    J Cardiovasc Pharmacol 59:29-36. 2012
    ..These data show that not only there are species-dependent properties in ion channel control of venomotor tone but also BK channels are required for rhythmic oscillations in venous tone...
  24. pmc Localization of NADPH oxidase in sympathetic and sensory ganglion neurons and perivascular nerve fibers
    Xian Cao
    The Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    Auton Neurosci 151:90-7. 2009
    ..The presence of a O(2)(-*)-generating enzyme in close vicinity to the sites of neurotransmitter handling in the nerve fibers suggests the possibility of novel redox-mediated mechanisms in peripheral neurovascular control...
  25. ncbi Differential expression of pancreatitis-associated protein and thrombospondins in arterial versus venous tissues
    Theodora Szasz
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    J Vasc Res 46:551-60. 2009
    ..To better characterize these expression patterns, and to identify candidate genes that could be manipulated selectively in the venous system, we performed whole genome expression profiling of arteries and veins...
  26. pmc Endothelin ET(B) receptors in arteries and veins: multiple actions in the vein
    Nathan R Tykocki
    Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences Bldg, East Lansing, MI 48824, USA
    J Pharmacol Exp Ther 329:875-81. 2009
    ..Moreover, the mechanisms of endothelial cell ET(B) receptor-mediated relaxation in RA and RVC are not the same...
  27. pmc Differential contributions of alpha-1 and alpha-2 adrenoceptors to vasoconstriction in mesenteric arteries and veins of normal and hypertensive mice
    ALEX A PEREZ-RIVERA
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Vascul Pharmacol 46:373-82. 2007
    ..This contribution of alpha(2)-ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE...
  28. ncbi Increased sympathetic venoconstriction and reactivity to norepinephrine in mesenteric veins in anesthetized DOCA-salt hypertensive rats
    Hui Xu
    Department of Pharmacology and Toxicology, Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    Am J Physiol Heart Circ Physiol 293:H160-8. 2007
    ..In DOCA-salt rats, in vivo ET-1 reactivity is maintained in MV, but reduced in MA...
  29. ncbi Morphological and biochemical characterization of remodeling in aorta and vena cava of DOCA-salt hypertensive rats
    Stephanie W Watts
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48823 1317, USA
    Am J Physiol Heart Circ Physiol 292:H2438-48. 2007
    ..These findings suggest that large veins may not undergo vascular remodeling in DOCA-salt hypertension...
  30. ncbi A comparison of arteries and veins in oxidative stress: producers, destroyers, function, and disease
    Theodora Szasz
    Department of Pharmacology and Toxicology, Michigan State University, B445 Life Sciences, East Lansing, MI 48825, USA
    Exp Biol Med (Maywood) 232:27-37. 2007
    ..Our understanding of the mechanisms underlying vascular diseases would greatly benefit from a more thorough exploration of the role of veins and venous oxidative stress...
  31. ncbi Activation of potassium channels by tempol in arterial smooth muscle cells from normotensive and deoxycorticosterone acetate-salt hypertensive rats
    Hui Xu
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA
    Hypertension 48:1080-7. 2006
    ..We conclude that upregulation of the BK channel alpha-subunit protein and tempol-induced increases in BK channel P(o) contribute to the enhanced depressor response caused by tempol in DOCA-salt hypertensive rats...
  32. ncbi In vitro continuous amperometry with a diamond microelectrode coupled with video microscopy for simultaneously monitoring endogenous norepinephrine and its effect on the contractile response of a rat mesenteric artery
    JinWoo Park
    Department of Chemistry, Department of Pharmacology and Toxicology, and the Neuroscience Program, Michigan State University, East Lansing, Michigan 48824, USA
    Anal Chem 78:6756-64. 2006
    ....
  33. ncbi Cyclooxygenase, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase MAPK, Rho kinase, and Src mediate hydrogen peroxide-induced contraction of rat thoracic aorta and vena cava
    Keshari Thakali
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    J Pharmacol Exp Ther 320:236-43. 2007
    ....
  34. ncbi Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function
    Keshari M Thakali
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    J Cardiovasc Pharmacol 47:742-50. 2006
    ..These data suggest that while NO deficiency increases oxidative stress and sympathetic activity in both arterial and venous vessels, the impact on veins does not make a major contribution to this form of hypertension...
  35. ncbi Differential trafficking and desensitization of human ET(A) and ET(B) receptors expressed in HEK 293 cells
    Xiaoling Dai
    Department of Pharmacology and Toxicology and Neuroscience Program, Life Science Building Room B308, Michigan State University, East Lansing, MI 48824, USA
    Exp Biol Med (Maywood) 231:746-51. 2006
    ..Finally, ET(A) and ET(B) receptors interact to change receptor trafficking which may modify ET receptor function in vascular SMCs coexpressing these receptors...
  36. ncbi Pleiotropic effects of hydrogen peroxide in arteries and veins from normotensive and hypertensive rats
    Keshari Thakali
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Hypertension 47:482-7. 2006
    ..In DOCA-salt hypertension, arterial but not venous contraction to H2O2 is enhanced, and relaxation to H2O2 is reduced...
  37. ncbi Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase
    Xiaoling Dai
    Department of Physiology, 2201 Biomedical and Physical Sciences Bldg, Michigan State University, East Lansing, Michigan 48824, USA
    Am J Physiol Heart Circ Physiol 290:H1019-26. 2006
    ..Thus elevated O2-* levels in hypertension may be a result of the increased activity of NADPH oxidase in postganglionic sympathetic neurons...
  38. ncbi Preferential myosin heavy chain isoform B Expression may contribute to the faster velocity of contraction in veins versus arteries
    Catherine M Rondelli
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48823, USA
    J Vasc Res 44:264-72. 2007
    ..9 +/- 1.2-fold higher in the aorta than vena cava. Thus, the SMB isoform is the predominant form expressed in rat veins, providing one possible mechanism for the faster response of veins to vasoconstrictors...
  39. pmc Determination of endogenous norepinephrine levels in different chambers of the rat heart by capillary electrophoresis coupled with amperometric detection
    Martin Novotny
    Department of Chemistry and the Neuroscience Program, Michigan State University, 320 Chemistry Building, East Lansing, MI 48824 1322, USA
    J Neurosci Methods 163:52-9. 2007
    ..65 pA at a detection potential of +0.86 V versus Ag/AgCl. A reproducible electrode response was observed for multiple injections of tissue homogenates with minimal response attenuation due to electrode fouling...
  40. ncbi Differential regulation of NADPH oxidase in sympathetic and sensory Ganglia in deoxycorticosterone acetate salt hypertension
    Xian Cao
    Department of Physiology, Michigan State University, East Lansing, MI 48824, USA
    Hypertension 50:663-71. 2007
    ..This differential regulation may contribute to unbalanced vasomotor control and enhanced vasoconstriction in the splanchnic circulation...
  41. pmc A comparison of reactive oxygen species metabolism in the rat aorta and vena cava: focus on xanthine oxidase
    Theodora Szasz
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA
    Am J Physiol Heart Circ Physiol 295:H1341-H1350. 2008
    ..We propose XO to be an important source for these differences. The result of this particular comparison may be reflective of a general arteriovenous contrast...
  42. pmc Impaired purinergic neurotransmission to mesenteric arteries in deoxycorticosterone acetate-salt hypertensive rats
    Stacie L Demel
    Neuroscience Program, B328 Life Science Building, Michigan State University, East Lansing, MI 48824, USA
    Hypertension 52:322-9. 2008
    ..These data highlight the potential importance of impaired purinergic regulation of arterial tone as a target for drug treatment of hypertension...
  43. pmc Cardiac norepinephrine transporter protein expression is inversely correlated to chamber norepinephrine content
    Erica A Wehrwein
    Dept of Physiology, Michigan State Univ, East Lansing, MI 48823, USA
    Am J Physiol Regul Integr Comp Physiol 295:R857-63. 2008
    ..In summary, there is a ventricular predominance of NET binding that corresponds to a high NE reuptake capacity in the ventricles, yet negatively correlates to tissue NE content...
  44. pmc Pharmacological endothelin receptor interaction does not occur in veins from ET(B) receptor deficient rats
    Keshari Thakali
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48823, USA
    Vascul Pharmacol 49:6-13. 2008
    ..Our data suggest that pharmacological ET A and ET B receptor interaction may be dependent on the presence of functional ET B receptors and independent of receptor location...
  45. ncbi Role of redox signaling and poly (adenosine diphosphate-ribose) polymerase activation in vascular smooth muscle cell growth inhibition by nitric oxide and peroxynitrite
    James Huang
    Department of Surgery, San Francisco Veteran s Affairs Medical Center, Division of Vascular Surgery, University of California, San Francisco, USA
    J Vasc Surg 47:599-607. 2008
    ..We sought to define the intracellular effects and signaling mechanisms of nitric oxide and peroxynitrite in smooth muscle cells...
  46. ncbi Diamond microelectrodes for in vitro electroanalytical measurements: current status and remaining challenges
    JinWoo Park
    Department of Chemistry, Michigan State University, East Lansing, MI 48824, USA
    Analyst 133:17-24. 2008
    ....
  47. ncbi CE coupled with amperometric detection using a boron-doped diamond microelectrode: validation of a method for endogenous norepinephrine analysis in tissue
    Veronika Quaiserová-Mocko
    Department of Chemistry, Michigan State University, East Lansing, MI, USA
    Electrophoresis 29:441-7. 2008
    ..1 +/- 5.6% (n = 6) from tissue homogenates. NE levels in the spleen, small intestine, and heart of a normotensive rat were found to be in the range of 0.77-0.97, 0.22-0.32, and 0.29-0.45 microg/g tissue (n = 3), respectively...
  48. ncbi Endothelium-targeted transgenic GTP-cyclohydrolase I overexpression inhibits neointima formation in mouse carotid artery
    Song Jie Liao
    Department of Pharmacology and Neurology, Neuroscience Program and Molecular Biology Program, Michigan State University, East Lansing, MI 48824 1317, USA
    Clin Exp Pharmacol Physiol 34:1260-6. 2007
    ..4. These findings suggest that the endothelial overexpression of GTPCH increased endothelial BH(4) synthesis and played a preventive role in neointimal formation induced by endothelium denudation...
  49. pmc Big ET-1 processing into vasoactive peptides in arteries and veins
    Stephanie W Watts
    Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824 1317, USA
    Vascul Pharmacol 47:302-12. 2007
    ..These results suggest at least one potential significant difference - the role of chymase - in in vitro enzymatic processing of big ET-1 in arteries and veins...
  50. pmc Differences in sympathetic neuroeffector transmission to rat mesenteric arteries and veins as probed by in vitro continuous amperometry and video imaging
    JinWoo Park
    Department of Chemistry and the Neuroscience Program, Michigan State University, East Lansing, MI 48824, USA
    J Physiol 584:819-34. 2007
    ..We conclude that there are fundamental differences in sympathetic neuroeffector mechanisms in MA and MV, which are likely to contribute to their different haemodynamic functions...
  51. ncbi Activation of ETB receptors increases superoxide levels in sympathetic ganglia in vivo
    Yanny E Lau
    Department of Pharmacology Toxicology, B327 Life Science, Michigan State University, East Lansing, MI 48824, USA
    Am J Physiol Regul Integr Comp Physiol 290:R90-5. 2006
    ..We conclude that ET(B) receptor activation in vivo significantly enhances O2- levels in sympathetic ganglia, due to both pressor effects and direct stimulation of ET(B) receptors in ganglion cells...

Research Grants30

  1. The Center for Native and Pacific Health Disparities Research
    MARJORIE K LEIMOMI MALA MAU; Fiscal Year: 2013
    ..5) To prepare and empower our diverse Native and Pacific People communities to take ownership of their own health and wellness. ..
  2. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  3. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  4. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  5. AMPK Endothelial Cell Dysfunction and the Metabolic Syndrome (PROGRAM PROJECT)
    Neil B Ruderman; Fiscal Year: 2013
    ..The proposed studies should both yield novel insights into the biological bases for the premature atherosclerosis and impaired angiogenesis associated with this entity and suggest new therapeutic targets for their prevention...
  6. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..