In experiments on the closed-chest dogs it was shown that NOS inhibition resulted in the significant alterations of hemodynamic indices (coronary and peripheral vascular resistance, cardiac output and heart rate) under local myocardial ischemia/reperfusion in comparison with control experiments. At the first time it was shown that NOS inhibition activated the autophagic destruction of cardiomyocytes in the ischemic myocardium and could reduce an area of functionally active myocardium. L-arginine administration attenuated cardio- and hemodynamic disturbances, that substantially improved the course of ischemia/reperfusion, diminished the ultrastructural changes in myocardium and prevented development of autophagic programmed cell death.
We investigated the inhibitory synaptic potentials (ISP) in isolated smooth muscle strips of the human duodenum circular layer from the ulcer adjacent region (I group) as well as ileum and distal part of small intestine, which were on a distance of some dozen centimeters from the place of disturbance under the different gastrointestinal diseases (II group). ISP amplitude was several times smaller in the muscle strips of the I group compare to the II group. It could depend on the alterations of smooth muscles cable properties, increase of connective tissue mass, changes in the intestinal nervous system and synaptic transmission in the region adjacent to duodenum ulcer. Pyridoxal-5'-phosphate effectively decreased amplitude and increased ISP latent period in the muscle strips from both groups. N(omega)-nitro-L-arginine, the blocker of NO-synthase did not affect pyridoxal-5'-phosphate activity in smooth muscles. Phosphate group was essential for realization of its influence on ISP in smooth muscles because pyridoxal did not influence both ISP amplitude and ISP latent period.
The aim of this study was to investigate coronary vascular responses, particularly NO-dependent, in the non-ischemic miocardium during local acute myocardial ischemia/reperfusion. The experiments were performed on the dogs with closed chest. Occlusion of a branch of the coronary artery resulted in a dilatation of the coronary vessels within the intact part of the myocardium. Neither inhibition of prostanoid production and KATP-channels, nor administration of atropine sulfate and dissection of the vagus nerve altered coronary dilatation within the non-ischemic myocardium. Whereas inhibition of NOS by L-NNA (50 mg/kg) completely changed it after coronary occlusion, furthermore coronary resistance temporally increased. Thus, the most reliable mechanism of that response was NO-dependent.
The effects of the NO donor sodium nitroprusside and the NO synthase blocker L-omega-N-nitroarginine (LNA) on body temperature, hypothalamic monoamines, and plasma corticosterone in conditions of cooling were studied in Male Wistar rats. Reductions in body temperature on cooling, both after administration of sodium nitroprusside and LNA, were no different from those seen without treatment. The basal corticosterone level after treatment with sodium nitroprusside increased from 5.3 +/- 2.2 to 29.1 +/- 1.8 microg%. Cooling led to a multiple increase in corticosterone levels in all animals, both in control conditions and after treatment with sodium nitroprusside and LNA. Sodium nitroprusside significantly decreased the basal hypothalamic noradrenaline level, by 37%. Cooling of the animals in these conditions led to an additional drop in the noradrenaline level. Noradrenaline levels 48 h after cold stress applied to animals cooled after treatment with LNA or sodium nitroprusside were significantly higher than in those cooled without treatment. No changes in serotonin and 5-hydroxyindoleacetic acid levels were seen in these experiments. The basal dihydroxyphenylacetic acid and dopamine levels increased after treatment with sodium nitroprusside, by 379% and 239% respectively. No dopamine response to cold was observed, though the dihydroxyphenylacetic acid level in the control group and animals treated with LNA increased. Thus, cold stress did not reveal differently directed directions for the actions of the NO donor and the NO synthase blocker, as seen with other types of stress.
PURPOSE: To investigate a possible role of the nitric oxide (NO)-cGMP signal transduction system in phagocytosis of rod outer segments (ROS) by cultured retinal pigment epithelial (RPE) cells. METHODS: Primary cultures of RPE cells from 10-day-old Brown Norway rats were used to study the phagocytosis of ROS by these cells. Phagocytosis of ROS was evaluated with or without an inhibitor of nitric oxide synthase (NOS), N(G)-nitro-L-arginine (L-NNA), and the reverse effects of L-NNA by L-arginine and 8-bromo-cGMP on phagocytosis were also studied. NO-associated cGMP production by RPE cells was monitored during phagocytosis using L-NNA. NOS activity was assayed in RPE cells and ROS to locate the source of NO. RESULTS: Phagocytosis of ROS was inhibited by L-NNA but not by D-NNA. L-NNA inhibited the ingestion in a dose-dependent manner, but not the binding of ROS. The inhibition was reversed by L-arginine and also by an NO donor, SIN-1. RPE cells challenged with ROS showed increased cGMP activity, which was significantly reduced by L-NNA and again restored by an overdose of L-arginine. NOS activity was found in RPE cells but not in ROS. CONCLUSIONS: Our data show that cGMP plays a role in the ingestion phase of ROS phagocytosis by RPE cells via a cGMP second-messenger system.
We investigated the influence of multiple introductions of NO precursor L-arginine and NOS non-selective blocker N-nitroL-arginine (NNLA) on thymic morpho-functional status in Wistar male rats with experimental diabetes mellitus (EDM). To reveal insulin-expressing, proliferating, Treg-cells, iNOS(+)-cells and Bcl-2(+)-cells, the immunohistochemical methods of direct and indirect immunofluorescence with monoclonal antibodies to insulin, PCNA, CD-25 antigen. Bcl-2 and iNOS of rat were used. It was established that NNLA administration to rats with EDM has more pronounced effect in comparison with L-arginine administration, demonstrating an increase in the number of Treg-cells, insulin-expressing and proliferating thymocytes and a decrease in the density of iNOS(+)- and Bcl-2(+)-cells population.