An increasing amount of experimental evidence supports the view that endothelium-derived factors and in particular, endothelium-derived relaxing factor (EDRF) takes part in the physiological control of cardiovascular functions. EDRF, identified as nitric oxide (NO) free radical, synthesized from L-arginine is involved in the control of blood pressure and platelet aggregation. It is also synthesized by cells other than endothelial cells including neurons. The proposed studies are designed to test the hypothesis, that endothelium-derived or neuronally synthesized nitric oxide influences cerebral blood flow, metabolism, flow/metabolism coupling, regional oxygen distribution and electrical activity of the cortex as well as cerebrovascular reactivity under physiological conditions and also in hemorrhagic hypotension. Specifically the studies are designed to examine the following questions. 1) Whether generalized blockade of the nitric oxide producing enzyme influences regional cerebral blood flow, metabolism and flow/metabolism coupling, oxygenation and electrical activity of the cerebral cortex as well as in vitro reactivity of the cerebral arteries. 2) To what extent neuronally synthesized versus endothelium-derived nitric oxide is responsible for these alterations. 3) To examine the role of the L- arginine-nitric oxide pathway in described alterations in cerebral metabolism, blood flow as well as in the oxygenation and electrocortical activity of the cortex during hemorrhagic hypotension. 4) Whether changes occur in the cerebrovascular endothelium-mediated responsiveness in hemorrhagic hypotension and shock, and to investigate the involvement of the nitric oxide pathway and the role of vasoactive mediators and neutrophil granulocytes in these changes. 5) To investigate whether alterations occur in cerebrocortical oxygen tension during NO blockade as well as in hypotension and shock. A better understanding of the physiological and pathological role of endothelium-derived vasoactive substances in different cerebral hypoxic and ischemic conditions such as shock and stroke could significantly contribute to the prevention and/or therapy of brain damage.
| Lohinai, Z; Balla, I; Marczis, J et al. (1996) The effect of a nitric oxide donor and an inhibitor of nitric oxide synthase on blood flow and vascular resistance in feline submandibular, parotid and pancreatic glands. Arch Oral Biol 41:699-704 |
| Lohinai, Z; Balla, I; Marczis, J et al. (1995) Evidence for the role of nitric oxide in the circulation of the dental pulp. J Dent Res 74:1501-6 |
| Szabo, C; Csaki, C; Benyo, Z et al. (1994) Effect of superoxide dismutase on hemorrhagic hypotension and retransfusion-evoked middle cerebral artery endothelial dysfunction. Circ Shock 44:104-10 |
| Kovach, A G; Lohinai, Z; Marczis, J et al. (1994) The effect of hemorrhagic hypotension and retransfusion and 7-nitro-indazole on rCBF, NOS catalytic activity, and cortical NO content in the cat. Ann N Y Acad Sci 738:348-68 |
