Different vasoactive effects of chronic endothelial and neuronal NO-synthase inhibition in young Wistar rats

While the unequivocal pattern of endothelial nitric oxide synthase (eNOS) inhibition in cardiovascular control is recognized, the role of NO produced by neuronal NOS (nNOS) remains unclear. The aim of this study was to compare the effects of chronic treatment with 7-nitroindazole (7-NI, nNOS inhibitor) and NG-nitro-l-arginine methylester (l-NAME, general and predominantly eNOS inhibitor) on cardiovascular system of young normotensive rats. Wistar rats (4 weeks old) were used: controls and rats administered either 7-NI (10 mg/kg bw/day) or l-NAME (50 mg/kg bw/day) in drinking water for 6 weeks. The systolic blood pressure (sBP) was measured by plethysmographic method, and the vasoactivity of isolated arteries was recorded. 7-NI-treatment did not affect sBP; however, the sBP was increased after l-NAME-treatment. l-NAME inhibited acetylcholine-induced relaxation of thoracic aorta (TA), whereas it remained unchanged after 7-NI-treatment. The response of TA to sodium nitroprusside was increased in both experimental groups. The expression of eNOS and nNOS in TA was unchanged in both experimental groups, whereas the activity of NOS was decreased in l-NAME-treated group. Noradrenaline- and angiotensin II-induced contractions of TA were reduced in l-NAME-treated group; however, the contractions remained unchanged in 7-NI-treated group. In all groups, the endogenous angiotensin II participated in adrenergic contraction of TA; this contribution was significantly increased in l-NAME-treated group. Neurogenic contractions in mesenteric artery (MA) remained unchanged after 7-NI-treatment, but increased after l-NAME-treatment. Results show that NO deficiency induced by administration of 7-NI and l-NAME had different cardiovascular effects: eNOS and nNOS triggered distinct signaling pathways in young normotensive rats

Insulin sensitivity and resistin expression in nitric oxide-deficient rats.

AIMS/HYPOTHESIS: The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. METHODS: Male Sprague-Dawley rats received [Formula: see text]-nitro-L: -arginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. RESULTS: Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.

Interacción óxido nítrico-dopamina: estudios farmacológicos y conductuales / Nitric oxide-dopamine interaction: pharmacological and behavioral studies

El óxido nítrico es una sustancia gaseosa de amplia difusión que presenta un mecanismo de acción único, capaz de afectar a numerosas células cercanas. Este gas desempeña un papel clave como neuromodulador. La evidencia experimental señala que entre los sistemas del óxido nítrico y dopaminérgico se produce una interacción, que ha sido objeto de un abundante número de investigaciones, principalmente en el cuerpo estriado. Los estudios conductuales indican la presencia de una interacción entre el sistema dopaminérgico y el óxido nítrico en el control del comportamiento motor. Los mecanismos mediante los cuales se produce esta interacción y sus resultados parecen depender de varios factores, entre ellos las condiciones del tejido, pero numerosos trabajos sugieren que, en condiciones fisiológicas, la transmisión dopaminérgica modula en algunas regiones la actividad óxido nítrico sintasa, y que el óxido nítrico regula la transmisión dopaminérgica, facilitándola. En este artículo se revisan los datos disponibles acerca de la interacción del óxido nítrico con el sistema dopaminérgico, los mecanismos propuestos a través de los cuales el óxido nítrico modula la liberación de dopamina y los trabajos conductuales que han puesto de manifiesto esta interacción

Nitric oxide is a widely diffused gaseous substance that presents a unique mechanism of action, capable of affecting numerous nearby cells. This gas plays a key role as a neuromodulator. Experimental evidence indicates that an interaction is produced between nitric oxide and dopaminergic systems, which has been the object of numerous investigations, mainly in the corpus striatum. Behavioral studies indicate that there is an interaction between the dopaminergic system and nitric oxide in the control of motor behavior. The mechanisms through which this interaction is produced and its results seem to depend on various factors, among them the tissular conditions, but several studies suggest that in physiological conditions dopaminergic transmission modulates nitric oxide synthase activity in some regions and that nitric oxide regulates dopaminergic transmission, facilitating it. The present article reviews the available data on the interaction between nitric oxide and the dopaminergic system, the proposed mechanisms through which nitric oxide modulates dopamine release and the behavioral studies which have reported this interaction

Computer model of hydroponics nutrient solution pH control using ammonium.

A computer simulation of a hydroponics-based plant growth chamber using ammonium to control pH was constructed to determine the feasibility of such a system. In nitrate-based recirculating hydroponics systems, the pH will increase as plants release hydroxide ions into the nutrient solution to maintain plant charge balance. Ammonium is an attractive alternative to traditional pH controls in an ALSS, but requires careful monitoring and control to avoid overdosing the plants with ammonium. The primary advantage of using NH4+ for pH control is that it exploits the existing plant nutrient uptake charge balance mechanisms to maintain solution pH. The simulation models growth, nitrogen uptake, and pH of a l-m2 stand of wheat. Simulation results indicated that ammonium-based control of nutrient solution pH is feasible using a proportional integral controller. Use of a 1 mmol/L buffer (Ka = 1.6 x 10(-6)) in the nutrient solution is required.

Nitrosyl hemoglobin in blood of normoxic and hypoxic sheep during nitric oxide inhalation.

During nitric oxide (NO) inhalation therapy, NO combines with deoxyhemoglobin to form nitrosyl hemoglobin (HbNO). We used electron spin resonance (ESR) spectroscopy to measure HbNO in arterial and mixed venous blood of normoxic and hypoxic sheep during NO inhalation. Our aim was to quantitatively measure HbNO levels in the blood during NO inhalation, because large amounts of HbNO reduce the oxygen capacity of blood, particularly in hypoxia. Another aim was to investigate the transfer of exogenous NO to the alpha-heme iron of hemoglobin. Thirteen sheep were anesthetized with pentobarbital sodium, and 60 parts per million (ppm) NO were administered for 1 h in the presence of normoxia and hypoxia. Two-way analysis of variance revealed that the HbNO level was dependent on the oxygen level (normoxia vs. hypoxia) and NO inhalation, and there was a significant negative correlation between the HbNO level and arterial O2 saturation (SaO2). Although the HbNO level increased during NO inhalation in hypoxia, the HbNO level at SaO2 > 60% was < 11 mumol/l monomer hemoglobin (0.11% of total 10 mmol/l monomer hemoglobin). The peak of the HbNO ESR spectrum in arterial blood is located in almost the same position in mixed venous blood with an asymmetric HbNO signal, indicating that the NO in beta-heme HbNO molecules had been transferred to alpha-heme molecules. The three-line hyperfine structure of HbNO on ESR spectra was distinct in venous blood in hypoxia during NO inhalation, indicating pentacoordinate alpha-NO heme formation in hypoxic blood. In conclusion, the amount of HbNO during 60 ppm NO inhalation did not considerably reduce the oxygen capacity of the blood even in the presence of hypoxia, and the NO of HbNO was transferred to the alpha-heme iron of hemoglobin, forming pentacoordinate alpha-NO heme in mixed venous blood in hypoxia.