It has been shown that nitric oxide (NO) increases aggression in male mice, whereas it decreases aggression in lactating female mice and prairie voles. It is also known that aggression can be exhibited at different levels in rodent species, strain or subtypes. The aims of this study were to investigate the proportion of aggressiveness in Wistar rats, the effect of intraperitoneally administered nonspecific nitric oxide synthase (NOS) inhibitor L-NAME (NG-nitro L-arginine methyl ester) on maternal aggression towards female intruders, and whether these effects are due to NO production or not. Rats were given saline intraperitoneally on the postpartum Day 2 and aggression levels were recorded. The same rats were given 60 mg/kg L-NAME or D-NAME (NG-nitro D-arginine methyl ester) on the postpartum Day 3 and their effects on aggression levels were compared to saline. While L-NAME administration did not cause any differences in the total number of aggressive behavior, aggression duration and aggression intensity, it reduced the proportion of animals showing aggressive behavior. In addition, the latency of the first aggression was significantly increased by L-NAME. In the D-NAME group, however, no significant change was found. Our results have shown that L-NAME reduces maternal aggression towards female intruders in Wistar rats through inhibition of NO production. These results suggest that the role of NO in offensive and defensive maternal aggression shares neural mechanisms., S. Ankarali, H. C. Ankarali, C. Marangoz., and Obsahuje seznam literatury
Glucagon and α-adrenergic-induced glycog enolysis is realized via the agonist/adenylyl cyclase/cAMP/protein kinase signaling pathway or via the activation of phosphorylase kinase by the mobilized calcium that supports the inhibition of glycogen synthase, respectively. The role of nitric oxide (NO) in this process has not been extensively studied. The present work was directed to the question whether NO is produced during glucagon-induced glycogenolysis in rat hepatocyte in a similar way like α-adrenoceptor stimulation. Glycogen-rich hepatocyte cultures were used. NO production (NO2-) was assessed under the influence of glucagon, dibutyryl cyclic AMP (db-cAMP), forskolin, the nitric oxide synthase (NOS) inhibitors Nω-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, and the NO donor S-nitroso-N-acetyl penicillamine (SNAP). Inducible NOS (iNOS) mRNA was examined by reverse transcription-polymerase chain reaction. Glycogenolysis was followed up by estimation of medium glucose levels. The amount of glucose and NO2- released by glycogen-rich hepatocytes was increased as a result of glucagon, db-cAMP, forskolin and SNAP treatments. iNOS gene expression was upregulated by glucagon. Glycogenolysis that occurs through glucagon receptor stimulation involves NO production downstream of transduction pathways through an isoform of NO synthase. The present and previous studies document possible involvement of NO signaling in glycogenolytic response to glucagon and adrenergic agonists in hepatocytes., H. Farghali, J. Hodis, N. Kutinová-Canová, P. Potměšil, E. Kmoníčková, Z. Zídek., and Obsahuje bibliografii a bibliografické odkazy
Hyperhomocysteinemia has been suggested to induce hypertension due to its role in endothelial dysfunction. However, it remains controversial whether homocysteine and hypertension are truly causally related or merely loosely associated. To test the hypothesis that hyperhomocysteinemia occurs in spontaneously hypertensive rats (SHR) we measured plasma levels of homocysteine in 10 male adult SHR and in 10 normotensive controls using ion exchange chromatography. In addition, plasma concentrations of the 22 most common amino acids were measured to explore the relation of homocysteine with amino acid metabolism. Plasma levels of homocysteine were significantly lower in SHR (4.1±0.1 μmol/l) than in controls (7.2±0.3 μmol/l) (p<0.00001). The amounts of aminobutyric acid, alanine, citrulline and valine were also decreased, whereas we found increased levels of aspartate, glutamate, glutamine, histidine and ornithine. Thus, contrary to our hypothesis, hypertension in SHR occurs despite low plasma levels of homocysteine. We provide a new hypothesis whereby reduced conversion of arginine to citrulline is related to increased ornithine levels, but decreased bioavailability of nitric oxide, resulting in impaired blood vessel relaxation and hypertension. In conclusion, our findings do not necessarily exclude that homocysteine and hypertension might be pathophysiologically connected, but corroborate the notion that hypertension can arise due to mechanisms independent of high homocysteine levels., D. Kondziella, H. Zetterberg, E. Haugen, M. Fu., and Obsahuje bibliografii a bibliografické odkazy
We studied the effect of thiazide-like diuretic – indapamide on fibrosis development in the left ventricle of young spontaneously hypertensive rats (SHR) and assessed the involvement of nitric oxide in this process. Six-week-old male SHR were treated with indapamide (1 mg/kg/day) for six weeks. Age-matched SHR were used as hypertensive and Wistar-Kyoto rats (WKY) as normotensive control. Systolic blood pressure was measured by tail-cuff plethysmography. Nitric oxide synthase (NOS) activity, protein expressions of endothelial (eNOS) and inducible NOS (iNOS), myocardial fibrosis and collagen type I and III were determined in the left ventricle. Indapamide treatment partially prevented SBP increase in SHR (SHR+Indapamide: 157±4, SHR: 171±3, WKY: 119±3 mmHg). Indapamide prevented myocardial fibrosis development in SHR, but without affecting collagen type I to type III ratio. Indapamide did not affect NOS activity as well as eNOS and iNOS protein expressions in the left ventricles evaluated by both Western blot and immunohistochemically. In conclusion, our results indicate that indapamide-induced prevention of myocardial fibrosis is not mediated by nitric oxide-related mechanism., P. Janega, S. Kojšová, L. Jendeková, P. Babál, O. Pecháňová., and Obsahuje bibliografii a bibliografické odkazy
High blood pressure (BP) of L-NAME hypertensive rats is maintained not only by the absence of nitric oxide (NO)-dependent vasodilatation but also by the enhancement of both sympathetic and angiotensin II-dependent vasoconstriction. The aim of the present study was to evaluate the role of inhibitory G (Gi) proteins, which are involv ed in tonic sympathetic vasoconstriction, in the pathogenesis of NO-deficient hypertension. We therefore studied BP response to chronic L-NAME administration (60 mg/kg/day for 4 weeks) in rats in which the in vivo inactivation of Gi proteins was induced by injection of pertussis toxin (PTX, 10 μg/kg i.v.). The impairment of sympathetic vasoconstriction due to PTX-induced Gi protein inactivation prevents the full development of NO-deficient hypertension because BP of PTX-treated rats subjected to chronic L-NAME administration did not reach hypertensive values. Nevertheless, chronic NO synthase inhibition per se is capable to increase moderately BP even in PTX-treated rats. Our data suggest that the sympathetic vasoconstriction is essential for the development of established NO-deficient hypertension., J. Zicha ... [et al.]., and Obsahuje seznam literatury
The nitric oxide/cGMP system has been shown to play a crucial role in the mechanism of learning and memory. The aim of the present study was to investigate whether the inhibition of NO synthase in brain regions leads to alterations of spontaneous behavior in rats. Male Wistar rats were treated with NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at the dose of 40 mg/kg/day. After 4 weeks of L-NAME treatment, NO synthase activity was significantly decreased by 75 % in the cerebellum, by 71 % in the cerebral cortex and by 72 % in the thoracic spinal cord. Decreased NO synthase activity in the nervous tissue was associated with decreased motor horizontal and vertical activities as well as by lowered frequency of sniffing, cleaning and defecation. It is concluded that the inhibition of NO synthase activity has a suppressive effect on spontaneous behavior of rats., L. Halčák, O. Pecháňová, Z. Žigová, L. Klemová, M. Novacký, I. Bernátová., and Obsahuje bibliografii
We analyzed the effect of FK 506 on the production of nitric oxide by macrophages. Isolated rat peritoneal macrophages were cultured for 24 h with or without lipopolysaccharide (LPS) (5 µg/ml) and in the absence or presence of FK 506 (0.1 and 1 µg/ml). The concentration of NO2- in culture supernatants was taken as a measure of nitric oxide production. FK 506 (0.1 and 1 µg/ml) reduced the LPS-induced increase of NO2- levels by 68 % and 81 %, respectively. The impact of cyclosporin A (CsA) was studied in order to compare their effects. CsA (0.1 and 1 µg/ml) decreased the levels of nitrites by 39 % and 69 %, respectively. The results obtained suggest that both immunosuppressive drugs exhibit a dose-dependent inhibitory effect on nitric oxide production and that FK 506 is a more potent agent than CsA in this respect., P. Střeštíková, B. Otová, M. Filipec, H. Farghali., and Obsahuje bibliografii
In experimental and human diabetes mellitus, evidence for an impaired function of the vascular endothelium has been found and has been suggested to contribute to the development of vascular complications in this disease. The aim of the study was to evaluate possible regional hemodynamic in vivo differences between healthy and diabetic rats which would involve nitric oxide (NO). Central hemodynamics and regional blood flow (RBF) were studied using radioactive microspheres in early streptozotocin (STZ)-diabetic rats and compared to findings in healthy control animals. This method provides a possibility to study the total blood flow and vascular resistance (VR) in several different organs simultaneously. L-NAME iv induced widespread vasoconstriction to a similar extent in both groups. In the masseter muscle of both groups, acetylcholine 2 μg/kg per min, induced a RBF increase, which was abolished by pretreatment with L-NAME, suggesting NO as a mediator of vasodilation. In the heart muscle of both groups, acetylcholine alone was without effect while the combined infusion of acetylcholine and L-arginine induced an L-NAME-sensitive increase in RBF. The vasodilation induced by high-dose acetylcholine (10 μg/kg per min) in the kidney was more pronounced in the STZ-diabetic rats. The results indicate no reduction in basal vasodilating NO-tone in the circulation of early diabetic rats. The sensitivity to vasodilating effects of acetylcholine at the level of small resistance arterioles vary between tissues but was not impaired in the diabetic rats. In the heart muscle the availability of L-arginine was found to limit the vasodilatory effect of acetylcholine in both healthy and diabetic rats. In conclusion, the results indicate a normal action of NO in the investigated tissues of the early STZ-diabetic rat., E. Granstam, S.-O. Granstam., and Obsahuje bibliografii
NO is the “hero” molecule of the last few decades. It is a ubiquitous and omnipotent radical with both hemodynamic and antiproliferative effects within the cardiovascular system. NO is an important counterregulatory factor for vasoconstrictors and growth promoting substances. Endothelial dysfunction with decreased NO production is related to many cardiovascular disorders, such as coronary artery disease, heart failure and hypertension. Despite the important role of NO within the circulation, there is only limited evidence in the form of large clinical trials that NO delivery can reduce cardiovascular morbidity and mortality. Thus, NO donors are not in the first line therapy in ischemic heart disease, heart failure or arterial hypertension and NO delivery is recommended only in particular clinical situations, when a well established treatment is contraindicated or has an insufficient effect. It is concluded that the insufficient NO production is the principal disorder in endothelial dysfunction, which is related to cardiovascular pathology with deteriorated prognosis, but the impact of therapeutically increased NO bioactivity on the morbidity and mortality is inferior to well established treatment with ACE-inhibitors, AT1 receptor blockers, beta-blockers, statins and certain antihypertensive drugs. There is little doubt that NO is king in the circulation, but kings seldom decide the battles., Fedor Šimko., and Obsahuje bibliografii
To investigate lisinopril effect on the contribution of nitric oxide (NO) and KCa channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensi ve WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K Ca channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SKCa and IKCa channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SKCa and BKCa proteins. Lisinopril treatment increased expression of eNOS, SKCa , BKCa channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SKCa and IKCa channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SKCa and IKCa channels is reduced, S. Albarwani, S. Al-Siyabi, I. Al-Husseini, A. Al-Ismail, I. Al-Lawati, I. Al-Bahrani, M. O. Tanira., and Obsahuje bibliografii