Harvey Weiss Professor UMDNJ Dept. of Physiology/Biophysics 675 Hoes Lane Room CB10 Piscataway. NJ 08854 (732) 235-4626 FAX - 5038 hweiss@umdnj.edu

How nitric oxide and its second messenger cyclic GMP serve as a "brake" on myocardial function and how this changes in disease. II. The relationship between excitatory amino acid receptors and cerebral oxygen supply and consumption balance and the changes in disease

In the heart. we are currently exploring the relationship between signal transduction and the control of local metabolism. We are focusing on the nitric oxide-cyclic GMP signal transduction system. which acts as a "brake" on myocardial function. This system exerts significant control of oxygen supply/consumption through direct effects on myocytes and vascular smooth muscle. We are attempting to determine the mechanisms through which this system operates and how problems like myocardial infarction. heart failure and obesity affect the responses to this system.

In the brain. excitatory amino acids. such as glutamate. increase cerebral oxygen consumption. The relative importance of the various glutamate receptors in the control of cerebral metabolism is not known. Activation of these receptors also affects cerebral blood flow. How the relationship between cerebral oxygen supply and consumption is affected by these receptors is not known. We also wish to determine the importance of the various receptor subtypes in the control of cerebral metabolism during stroke. Excess activation of these receptors leads to excitotoxicity.

Selected Publications

Tan T, Luciano JA, Scholz PM, Weiss HR. (2009) Hypoxia inducible Factor-1 improves the actions of positive inotropic agents in stunned cardiac myocytes. Clin Exp Pharmacol Physiol. Mar 2. [Epub ahead of print]

Zhang Q, Davidov T, Weiss HR, Scholz PM. (2009) SERCA inhibition limits the functional effects of cyclic GMP in both control and hypertrophic cardiac myocytes. Pharmacology. 83(4):223-30.

Chi OZ, Hunter C, Liu X, Weiss HR. (2009) Effects of exogenous excitatory amino acid neurotransmitters on blood-brain barrier disruption in focal cerebral ischemia. Neurochem Res. 34(7):1249-54.

Chi OZ, Hunter C, Liu X, Tan T, Weiss HR. (2008) Effects of VEGF on the blood-brain barrier disruption caused by hyperosmolarity. Pharmacology. 82(3):187-92.

Luciano JA, Tan T, Zhang Q, Huang E, Scholz P, Weiss HR. (2008) Hypoxia inducible factor-1 improves the actions of nitric oxide and natriuretic peptides after simulated ischemia-reperfusion. Cell Physiol Biochem. 21(5-6):421-8.

Chi OZ, Hunter C, Liu X, Weiss HR. (2008) Effects of erythropoietin on blood-brain barrier disruption in focal cerebral ischemia. Pharmacology. 82(1):38-42.

Weiss HR, Liu X, Chi OZ. (2008) Cerebral O(2) consumption in young Eker rats, effects of GABA blockade: implications for autism. Int J Dev Neurosci. 26(5):517-21.

Chi OZ, Hunter C, Liu X, Weiss HR. (2008) Effects of deferoxamine on blood-brain barrier disruption and VEGF in focal cerebral ischemia. Neurol Res. 30(3):288-93.

Zhang Q, Scholz PM, Pilzak A, Su J, Weiss HR. (2007) Role of phospholamban in cyclic GMP mediated signaling in cardiac myocytes. Cell Physiol Biochem. 20(1-4):157-66.

Weiss HR, Liu X, Zhang Q, Chi OZ. (2007) Increased cerebral oxygen consumption in Eker rats and effects of N-methyl-D-aspartate blockade: Implications for autism. J Neurosci Res. 85(11):2512-7.

Chi OZ, Hunter C, Liu X, Weiss HR. (2007) Effects of anti-VEGF antibody on blood-brain barrier disruption in focal cerebral ischemia. Exp Neurol. 204(1):283-7.

Davidov T, Weiss HR, Tse J, Scholz PM. (2006) Chronic nitric oxide synthase blockade desensitizes the heart to the negative metabolic effects of nitric oxide.
Life Sci. 79(17):1674-80.

Katz E. Zhang Q. Weiss HR. Scholz PM. (2006) T4-induced cardiac hypertrophy disrupts cyclic GMP mediated responses to brain natriuretic peptide in rabbit myocardium. Peptides. 27(9):2276-83.

Zhang Q. Goel N. Rodriguez R. Scholz PM. Weiss HR. (2006) Importance of ryanodine receptors in effects of cyclic GMP is reduced in thyroxine-induced cardiac hypertrophy. Eur J Pharmacol. 537(1-3):45-51.

Moalem J. Davidov T. Zhang Q. Grover GJ. Weiss HR. Scholz PM. (2006) Negative inotropic effects of C-Type natriuretic peptide are attenuated in hypertrophied ventricular myocytes associated with reduced cyclic GMP production. J Surg Res. Apr 4; [Epub ahead of print]

Moalem J. Weiss HR. Davidov T. Rodriguez R. Molino B. Lazar MJ. Scholz PM. (2006) Heart Failure Reduces Both the Effects and Interaction Between Cyclic GMP and Cyclic AMP. J Surg Res. Mar 15; [Epub ahead of print]

Chi OZ. Hunter C. Liu X. Weiss HR. (2005)Effects of VEGF and nitric oxide synthase inhibition on blood-brain barrier disruption in the ischemic and non-ischemic cerebral cortex. Neurol Res. 27(8):864-8.

Zhang S. Rodriguez R. Scholz PM. Weiss HR. (2006) Functional interaction of a beta-adrenergic agonist and cyclic GMP phosphodiesterase inhibitor in control and hypertrophic cardiomyocytes. Pharmacology. 76(2):53-60.

Su J. Tse J. Scholz PM. Weiss HR. (2005) Alterations in ventricular myocyte contraction caused by C-type natriuretic peptide and nitric oxide in eNOS-/- mice. J Mol Cell Cardiol. 39(6):920-8.

Moalem J. Davidov T. Katz E. Scholz PM. Weiss HR. (2005) Atrial natriuretic peptide reverses the negative functional effects of stunning in rabbit myocardium. Regul Pept. 132(1-3):47-52.

Zhang S. Grover GJ. Stokes H. Scholz PM. Weiss HR. (2005) Negative inotropic effect of low-dose ethanol in mouse ventricular myocytes is mediated by activation of endothelial nitric oxide synthase. J Cardiovasc Pharmacol. 46(3):343-7.

Zhang Q. Lazar M. Molino B. Rodriguez R. Davidov T. Su J. Tse J. Weiss HR. Scholz PM. (2005) Reduction in interaction between cGMP and cAMP in dog ventricular myocytes with hypertrophic failure. Am J Physiol Heart Circ Physiol. 289(3):H1251-7.

Weiss HR. Katz E. Tse J. Scholz PM. (2005) Negative metabolic effects of cGMP are enhanced in obese rat hearts. J Cardiovasc Pharmacol. 45(6):533-8.

Su J. Scholz PM. Weiss HR. (2005) Differential effects of cGMP produced by soluble and particulate guanylyl cyclase on mouse ventricular myocytes. Exp Biol Med (Maywood). 230(4):242-50.

Zhang Q. Moalem J. Tse J. Scholz PM. Weiss HR. (2005) Effects of natriuretic peptides on ventricular myocyte contraction and role of cyclic GMP signaling. Eur J Pharmacol. 510(3):209-15.

Zhang Q. Scholz PM. He Y. Tse J. Weiss HR. (2005) Cyclic GMP signaling and regulation of SERCA activity during cardiac myocyte contraction. Cell Calcium. 37(3):259-66.

Su J. Scholz PM. Tse J. Weiss HR. (2004) Effects of cyclic GMP and its protein kinase on the contraction of ventricular myocytes from hearts after cardiopulmonary arrest. Can J Physiol Pharmacol. 82(11):986-92.

Su J. Zhang Q. Moalem J. Tse J. Scholz PM. Weiss HR. (2005) Functional effects of C-type natriuretic peptide and nitric oxide are attenuated in hypertrophic myocytes from pressure-overloaded mouse hearts. Am J Physiol Heart Circ Physiol. 288(3):H1367-73.

Goldenthal MJ. Weiss HR. Marin-Garcia J. (2004) Bioenergetic remodeling of heart mitochondria by thyroid hormone. Mol Cell Biochem. 265(1-2):97-106.

Liu X. Chi OZ. Weiss HR. (2004) Effects of metabotropic glutamate receptor stimulation on blood-brain barrier permeability during focal cerebral ischemia. Neurochem Res. 29(10):1857-62.

Zhang Q. Lazar M. Yan L. He Y. Tse J. Weiss HR. Scholz PM. (2004) Cyclic GMP reduces myocardial stunning through non-cyclic GMP protein kinase mechanisms. J Cardiovasc Pharmacol. 44(2):235-43.

Sinha AK. Azevedo R. Chi OZ. Weiss HR. (2004) Down-regulation of AMPA glutamate receptors reduces cerebrocortical metabolic response to stimulation. Neurochem Res. 29(7):1425-30.

Rodriguez R. Molino B. Weiss HR. Scholz PM. (2004) Negative metabolic and coronary flow effects of decreases in cAMP and increases in cGMP in control and renal hypertensive rabbit hearts. J Appl Physiol. 97(1):439-45.

Yan L. Zhang Q. Scholz PM. Weiss HR. (2003) Cyclic GMP protein kinase activity is reduced in thyroxine-induced hypertrophic cardiac myocytes. Clin Exp Pharmacol Physiol. 30(12):943-50.

Liu X. Chi OZ. Weiss HR. (2003) Effects of metabotropic glutamate receptor stimulation on cerebral O2 consumption and blood flow during focal cerebral ischemia in rats. Neurochem Res. 28(12):1799-804.

Weiss HR. Lazar MJ. Punjabi K. Tse J. Scholz PM. (2003) Negative functional effects of cyclic GMP are altered by cyclic AMP phosphodiesterases in rabbit cardiac myocytes. Eur J Pharmacol. 481(1):25-31.

Vaks YK. Weiss HR. Liu X. Chi OZ. (2003) 17 Beta-estradiol suppresses AMPA-induced increases in regional cerebral O2 consumption. Neurol Res. 25(7):754-8.

Tse J. Gandhi A. Yan L. He YQ. Weiss HR. (2003) Effects of triiodothyronine pretreatment on beta-adrenergic responses in stunned cardiac myocytes. J Cardiothorac Vasc Anesth. 17(4):486-90.

Weiss HR. Gandhi A. Scholz PM. (2003) Negative effect of nitric oxide on shortening-frequency relationship in cardiac myocytes is diminished after simulated ischemia-reperfusion. Basic Res Cardiol. 98(5):311-8.

Su J. Zhang S. Tse J. Scholz PM. Weiss HR. (2003) Alterations in nitric oxide-cGMP pathway in ventricular myocytes from obese leptin-deficient mice. Am J Physiol Heart Circ Physiol. 285(5):H2111-7.