Local and cardiorenal effects of periodontitis in nitric oxide-deficient hypertensive rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

iNOS-Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nitric oxide modulates the cardiovascular effects elicited by acetylcholine in the NTS of awake rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Subfornical organ mediates pressor effect of angiotensin: Influence of nitric oxide synthase inhibitors, AT(1) and AT(2) angiotensin antagonist's receptors

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Endodontic Chelators Induce Nitric Oxide Expression by Murine-cultured Macrophages

Introduction: Endodontic chelators may extrude to apical tissues during instrumentation activating cellular events on periapical tissues. This study assessed in vitro the expression of nitric oxide (NO) concentrations by murine peritoneal macrophages after contact with MTAD (Dentsply/Tulsa, Tulsa, OK), Tetraclean (Ogna Laboratori Farmaceutici, Muggio, Italy), Smear Clear (Sybron Endo, Orange, CA), and EDTA (Biodinamica, Ibipora, PR, Brazil). Methods: Macrophage cells were obtained from Swiss mice after peritoneal lavage. Chelators were diluted in distilled water obtaining 12 concentrations, and MTT assay identified the concentrations, per group, displaying the highest cell viability (analysis of variance, p < 0.01). Selected concentrations were tested for NO expression using Griess reaction. Culture medium and lipopolysaccharide (LPS) were used as controls. Results: Analysis of variance and Tukey tests showed that all chelators displayed elevated NO concentrations compared with the negative control (p < 0.01). MTAD induced the lowest NO expression, followed by Tetraclean, EDTA, and Smear Clear. No difference was observed between MTAD and Tetraclean (p > 0.01), Tetraclean and EDTA (p > 0.01), and EDTA and Smear Clear (p > 0.01). LPS ranked similar to both EDTA and Smear Clear (p > 0.01). Conclusion: The tested endodontic chelators displayed severe proinflammatory effects on murine-cultured macrophages. Citric acid-based solutions induce lower No release than EDTA-based irrigants. (J Endod 2009;35:824-828)

The sympathetic adrenomedullary system, but not the hypothalamic-pituitary-adrenal axis, participates in aorta adaptive response to stress: nitric oxide involvement

Stress induced a decrease in the reactivity of the aorta to noradrenaline (NA), as a consequence of an endothelial nitric oxide (NO) system hyperactivity. The main characteristic of the stress response is activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic adrenomedullary (SA) system. The participation of the HPA axis and SA system in the decreased reactivity to NA in the aorta of rats exposed to 4-h immobilization was investigated. Concentration-response relationships for NA were obtained in the aorta, with and without endothelium, isolated from normal and stressed rats, following these procedures: (1) in the absence and presence of L-NAME; (2) after adrenalectomy (ADX) or not, in the absence or presence of L-NAME; (3) ADX rats treated or not with corticosterone; (4) ADX associated with stress; and (5) treated or not with reserpine. The reactivity of aorta without endothelium was unaffected by the procedures. The reactivity of aorta with endothelium was decreased by either stress or ADX. This effect was reversed by both L-NAME and corticosterone. ADX did not potentiate the decrease in the aorta reactivity induced by stress. Reserpine did not change the reactivity of aorta with endothelium from normal rats, but prevented the decrease in reactivity induced by stress. It is concluded that the HPA axis participates in endothelium-dependent modulation of aorta reactivity in normal conditions and that thr SA system participates in hyperactivity of the endothelial NO-system induced by stress, which is responsible for the decreased aorta reactivity to NA. (C) 2000 Elsevier B.V. B.V. All rights reserved.

Gastroprotective effect of Cissus sicyoides (Vitaceae): Involvement of microcirculation, endogenous sulfhydryls and nitric oxide

Aim of the study: Cissus sicyoides L. is a medicinal plant popularly known in Brazil against various diseases and the research interest in this plant is justifiable because of its potential medicinal value in stomachache and gastric ulcer.Materials and methods: The methanolic extract obtained from the leaves of Cissus sicyoides (Cc) was evaluated for the ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH, absolute ethanol, piroxicam and pylorus ligature) in rodents. We also evaluated microcirculation, antioxidant action and participation of NO (nitric oxide) and sulfhydryls (SH) groups in the Cc gastroprotective action.Results: Administration of Cc significantly reduced gastric lesions induced by different ulcerogenic agents in rodents. This extract administered by oral route significantly increased gastric volume without exerting antisecretory effect. The Cc effect involved an increase of the defense mechanism of the gastrointestinal mucosa such as NO and SH groups that prevent and attenuate the ulcer process. The Cc also has antioxidant property against oxidative stress but does not modify microcirculation response in gastric mucosa.Conclusions: These results confirmed the traditional use of Cissus sicyoides for the treatment of gastric ulcer. (C) 2008 Elsevier B.V. All rights reserved.

Perinatal lead exposure affects nitric oxide and cyclooxygenase pathways in aorta of weaned rats

Perinatal Pb exposure may modulate arterial tone through nitric oxide (NO) and cyclooxygenase products. To investigate this, Wistar dams received 1000 ppm of Pb or sodium acetate (control) in drinking water during pregnancy and lactation. Curves were constructed in phenylephrine-precontracted intact and/or denuded rings of thoracic aortas of weaned (23-day-old) male pups from their responses to N-omega-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and ACh in the absence or presence of indomethacin (10(-5)M, cyclooxygenase inhibitor) or L-NAME (3 x 10(-7)M and 3 x 10(-4)M). Blood lead concentration and systolic blood pressure (SBP) were higher in intoxicated than control pups (blood lead mu g/dl: control < 3.0, Pb 58.7 +/- 6.5*; SBP mmHg: control 111.4 +/- 2.3, Pb 135.5 +/- 2.4*). In L-NAME-treated rings maximal responses increased in Pb-exposed rats, and were higher in intact than in denuded aortas (contraction [% of phenylephrine] intact: control 184.3 +/- 23.7, Pb 289.1 +/- 18.3*; denuded: control 125.1 +/- 4.5, Pb 154.8 +/- 13.3*). ACh-induced relaxation in intact aortas from Pb-exposed rats presented rightward shift in L-NAME presence (EC50 x 10(-7)M: control 1.32 [0.33-5.18], Pb 4.88 [3.56-6.69]*) but moved left under indomethacin (EC50 x 10(-7)M: control 8.95 [3.47-23.07], Pb 0.97 [0.38-2.43]*). *p < 0.05 significant relative to the respective control; N = 7-9. Endothelium removal abolished ACh-induced relaxation. Perinatal Pb exposure caused hypertension associated with alterations in the production and/or release of basal and stimulated endothelium-derived relaxing factors-NO and constricting cyclooxygenase products. These findings may help explain the contribution of NO and cyclooxygenase products to the etiology and/or maintenance of Pb-induced hypertension and could ultimately lead to therapeutic advantages in plumbism.

Gastroprotective mechanisms of Citrus lemon (Rutaceae) essential oil and its majority compounds limonene and beta-pinene: Involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, sulfhydryl compounds, nitric oxide and prostaglandin E-2

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Gastroprotective Effect of Serjania erecta Radlk (Sapindaceae): Involvement of Sensory Neurons, Endogenous Nonprotein Sulfhydryls, and Nitric Oxide

The present study reveals the pharmacological action of Serjania erecta Radlk. (Family Sapindaceae), an important medicinal plant species used in the Brazilian Pantanal against gastric pain. The methanolic (Me) and chloroformic (Se) extracts obtained from leaves of S. erecta were challenged by a very strong necrotizing agent in rodents, absolute ethanol. Se was also confronted with a nitric oxide synthase inhibitor (N(G)-nitro-l-arginine methyl ester), a capsaicin cation channel transient receptor potential vanilloid type 1 antagonist (ruthenium red), or a sulfhydryl-blocker (N-ethylmaleimide) to evaluate the participation of these cytoprotective factors in gastroprotection. In an in vivo experimental model, Me and Se presented several degrees of gastroprotective action without signs of acute toxicity. The best gastroprotective effect was restricted to all doses of Se. The mechanisms involving the gastroprotective action of Se are related to an augmented defense mechanism of the gastrointestinal mucosa consisting of sensory neurons, nitric oxide, and sulfhydryl groups that prevent and attenuate the ulcer process. The presence of polyisoprenoids in the Se explains the potent gastroprotective action of this medicinal species. Effective gastroprotective action and the absence of acute toxicity indicate this species may be a promising herbal drug against gastric disease.

Involvement of Glutathione, Sulfhydryl Compounds, Nitric Oxide, Vasoactive Intestinal Peptide, and Heat-Shock Protein-70 in the Gastroprotective Mechanism of Croton cajucara Benth. (Euphorbiaceae) Essential Oil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of a leukotriene inhibitor (MK886) on nitric oxide and hydrogen peroxide production by macrophages of acutely and chronically stressed mice

We evaluated the effect of a leukotriene inhibitor (MK886) on nitric oxide (NO) and hydrogen peroxide (H2O2) production by peritoneal macrophages of mice subjected to acute and chronic stress. Acute stress was induced by keeping mice immobilized in a tube for 2 h. Chronic stress was induced over a 7-day period by the same method, but with increasing duration of immobilization. The effects of MK886 were investigated in-vitro after incubation with peritoneal macrophages, and in-vivo by submitting mice to stress and treating them daily with MK886. Supernatants of macrophage cultures were collected for NO determination and adherent cells were used for H2O2 determination. Macrophages from mice submitted to acute or chronic stress showed no alterations in H2O2 production. However, macrophages of acutely and chronically stressed mice showed inhibition of NO after incubation with MK886 in-vitro. Administration of MK886 to chronically stressed mice increased generation of H2O2 and inhibited production of NO. Our data suggest an important role of leukotrienes in NO synthesis, which is important in controlling replication of several infectious agents, mainly in stressed and immunosuppressed animals.

Nitric oxide synthase activity in tissues of the blowfly Chrysomya megacephala (Fabricius, 1794)

Although insects lack the adaptive immune response of the mammalians, they manifest effective innate immune responses, which include both cellular and Immoral components. Cellular responses are mediated by hemocytes, and Immoral responses include the activation of proteolytic cascades that initiate many events, including NO production. In mammals, nitric oxide synthases (NOSs) are also present in the endothelium, the brain, the adrenal glands, and the platelets. Studies on the distribution of NO-producing systems in invertebrates have revealed functional similarities between NOS in this group and vertebrates. We attempted to localize NOS activity in tissues of naive (UIL), yeast-injected (YIL), and saline-injected (SIL) larvae of the blowfly Chrysomya megacephala, using the NADPH diaphorase technique. Our findings revealed similar levels of NOS activity in muscle, fat body, Malpighian tubule, gut, and brain, suggesting that NO synthesis may not be involved in the immune response of these larval systems. These results were compared to many studies that recorded the involvement of NO in various physiological functions of insects.

Nitric oxide in plants: a brief discussion on this multifunctional molecule

Diversos estudos vêm sendo realizados com a finalidade de aumentar o conhecimento sobre a ocorrência e a atividade do óxido nítrico (ON) nas plantas. Nesse sentido, a presente revisão objetivou abordar alguns aspectos referentes ao on nas plantas, tais como propriedades químicas, vias de síntese, efeitos fisiológicos, ação antioxidante, transdução do sinal, interação com hormônios vegetais e expressão gênica. Nos últimos anos, muitos avanços têm sido obtidos em relação à síntese de on e seus efeitos fisiológicos nas plantas. Porém, os mecanismos moleculares que fundamentam seus efeitos permanecem pouco compreendidos. É sinalizada uma investigação em detalhes sobre as estreitas interações entre ON, Ca2+, ADP-ribose cíclica (cADPR) e proteínas quinases. Além disso, ainda não foi possível identificar uma enzima vegetal que apresente atividade semelhante à da óxido nítrico sintase (NOS). A elucidação de tais aspectos representa um desafio para futuros trabalhos.