Susana Gorzalczany

Evaluation of antinociceptive, antinflammatory activities and phytochemical analysis of aerial parts of Urtica urens L.

The antinociceptive and antiinflammatory activities of the ethanol extract of the aerial part of Urtica urens were determined by experimental animal models. U. urens extract was found to possess significant antinociceptive activity in chemically induced mouse pain models (ED50 39.3 mg/kg: 17.2–74.5 mg/kg) in the writhing test and 62.8% inhibition of the licking time in the late phase of the formalin test at a dose of 500 mg/kg p.o. and antiinflammatory activity on carrageenan‐induced rat hind paw edema (41.5% inhibition at a dose of 300 mg/kg i.p.). The extract displayed activity neither in the thermal model of pain nor in the topical inflammation model. The major component of the extract was determined as chlorogenic acid (670 mg/1000 g dry weight) and could be partly responsible for this activity. Copyright

Angiotensin-(1-7) inhibits the angiotensin II-enhanced norepinephrine release in coarcted hypertensive rats.

Since it has been suggested that angiotensin (Ang) (1-7) functions as an antihypertensive peptide, we studied its effect on the Ang II-enhanced norepinephrine (NE) release evoked by K+ in hypothalami isolated from aortic coarcted hypertensive (CH) rats. The endogenous NE stores were labeled by incubation of the tissues with 3H-NE during 30 min, and after 90 min of washing, they were incubated in Krebs solution containing 25 mM KCl in the absence or presence of the peptides. Ang-(1-7) not only diminished the K+-evoked NE release from hypothalami of CH rats, but also blocked the Ang II-enhanced NE release induced by K+. Ang-(1-7) blocking action on the Ang II response was prevented by [D-Ala7]Ang-(1-7), an Ang-(1-7) specific antagonist, by PD 123319, an AT2-receptor antagonist, and by Hoe 140, a B2 receptor antagonist. Ang-(1-7) inhibitory effect on the Ang II facilitatory effect on K+-stimulated NE release disappeared in the presence of Nomega-nitro-L-arginine methylester and was restored by L-arginine. Our present results suggest that Ang-(1-7) may contribute to blood pressure regulation by blocking Ang II actions on NE release at the central level. This inhibitory effect is a nitric oxide-mediated mechanism involving AT2 receptors and/or Ang-(1-7) specific receptors and local bradykinin generation.

Vicenin-2, a potential anti-inflammatory constituent of Urtica circularis.

Vicenin-2 (1), a flavonoid glycoside, was isolated and identified from an ethanol extract of the aerial parts of Urtica circularis. This crude extract was found to possess significant anti-inflammatory activity in a carrageenan-induced rat hind paw edema model (41.5% inhibition at a dose of 300 mg/kg; ip). The effects of 1 on several inflammatory mediators were investigated. In cultured murine macrophages, this compound modified LPS-induced total nitrite and TNF-α production, in addition to the LPS-induced translocation of the nuclear factor NF-κB.

Antinociceptive effect of some Argentine medicinal species of Eupatorium.

Eupatorium laevigatum, E. arnottianum and E. subhastatum, plants used in Argentine folk medicine for the treatment of inflammation and pain related problems, were evaluated for analgesic activity. The infusions of these species (500 mg/kg, p.o.) produced a reduction in the number of stretches of 46.6%, 41.5% and 35.6% respectively, in the acetic acid induced writhing test. This antinociceptive effect of the infusions was not reversed by pretreatment with naloxone. The infusions studied did not produce antinociceptive effects when assayed in the hot plate test. These results suggest that the analgesic activity is exerted by a mechanism unrelated to interaction with opioid systems.

Angiotensin II Regulates Cardiac Hypertrophy via Oxidative Stress but Not Antioxidant Enzyme Activities in Experimental Renovascular Hypertension

The aim of this study was to provide new insights into the role of angiotensin II and arterial pressure in the regulation of antioxidant enzyme activities in a renovascular model of cardiac hypertrophy. For this purpose, aortic coarcted rats were treated with losartan or minoxidil for 7 days. Angiotensin II induced cardiac hypertrophy and oxidative stress via Nox4, p22phox and p47phox, which are components of the NAD(P)H oxidase. Antioxidant enzymes were regulated by arterial pressure and were not implicated in cardiac hypertrophy. Heme oxygenase-1, the rate-limiting enzyme in heme catabolism, behaved as a catalase and glutathione peroxidase, and is regulated by arterial pressure. In summary, the present report indicates that cardiac hypertrophy, induced by renovascular hypertension, depends on angiotensin II through reactive oxygen species and is not prevented by the action of antioxidant enzymes.

Controversy about COOPERATE ABPM Trial Data

mm Hg, 63% between 120 and 150 mm Hg, and the remaining 19% more than 150 mm Hg. A similar incidence was observed among treatment groups. Interestingly, the high variability of the systolic BP values was more characteristic among patients who were able to effectively restrict their salt intake. As compared with the systolic values, the nighttime values were constant throughout the measurements, partly because the drugs were taken at night or bedtime. Naoyuki Nakao, MD, PhD Division of Nephrology Rokko Island Hospital Koh-Yoh Cho Naka 2-11 Higashinada, Kobe, Japan

Metabolites from endophytes of the medicinal plant Erythrina crista-galli

Erythrina crista-galli (Fabaceae) is used in Argentinean ethnopharmacology as anti-inflammatory medication, narcotic, desinfectant, and for the treatment of wounds. The common name of the tree is “ceibo“ or coral tree. The dominating endophytes in E. crista-galli all belong to the genus Phomopsis as identified by microscopic features and the analysis of their ITS sequences. To investigate a possible contribution of Phomopsis spp. to the metabolites found in the plant, twelve different isolates were cultivated in different media. Besides several new metabolites a number of known compounds were detected: mellein, nectriapyrone, 4-hydroxymellein, scytalone, tyrosol, clavatol, mevinic acid, and mevalonolactone.

Increased hypothalamic angiotensin-(1-7) levels in rats with aortic coarctation-induced hypertension.

Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process.

Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload

The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up‐regulation of pro‐inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague–Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg−1 in bolus) (Na–Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min−1 kg−1) (Na–Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FENa) were measured. Ang II, NF‐κB, hypoxia inducible factor‐1α (HIF‐1α), transforming growth factor β1 (TGF‐β1), smooth muscle actin (α‐SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF‐κB, and TGF‐β1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF‐1α immunostaining, lower eNOS expression, and unmodified α‐SMA. Losartan and tempol increased FENa in sodium overload group. Although losartan reduced Ang II and NF‐κB staining and increased eNOS expression, it did not restore HIF‐1α expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF‐1α expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF‐1α and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF‐1α expression and down‐regulating TGF‐β1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. J. Cell. Physiol. 224:41–48, 2010

Renal Protective Role of Atrial Natriuretic Peptide in Acute Sodium Overload-Induced Inflammatory Response

Background: The present study was performed to explore the effect of exogenous infusions of atrial natriuretic peptide (ANP) on the early inflammatory response during acute sodium overload in normal rats. Methods: Sprague Dawley rats were exposed to acute sodium overload (Na 1.5 M). Nonhypotensive doses of ANP (1 and 5 µg ·kg–1 ·h–1) were infused simultaneously with sodium or after sodium infusion in order to evaluate prevention or reversion of the inflammatory response, respectively. We determined inflammation markers in renal tissue by immunohistochemistry. Results: Creatinine clearance was not reduced in any case. Sodium tubular reabsorption increased after sodium overload (334.3 ± 18.7 vs. control 209.6 ± 27.0 mEq·min–1, p < 0.05) without changes in mean arterial pressure. This increase was prevented (228.9 ± 26.4; p < 0.05) and reversed (231.5 ± 13.9; p < 0.05) by ANP-5 µg ·kg–1 ·h–1. Sodium overload increased the expression of: RANTES (38.4.3 ± 0.8 vs. 2.9 ± 0.6%, p < 0.001), transforming-growth-factor-β1 (35.3 ± 1.0 vs. 5.0 ± 0.7%, p < 0.001), α-smooth muscle actin (15.6 ± 0.7 vs. 3.1 ± 0.3%, p < 0.001), NF-ĸB (9.4 ± 1.3 to 2.2 ± 0.5 cells/mm2, p < 0.001), HIF-1α (38.2 ± 1.7 to 8.4 ± 0.8 cells/mm2, p < 0.001) and angiotensin II (35.9 ± 1.3 to 8.2 ± 0.5%, p < 0.001). ANP-5 µg ·kg–1 ·h–1 prevented and reversed inflammation: RANTES (9.2 ± 0.5 and 6.9 ± 0.7, p < 0.001); transforming growth factor-β1 (13.2 ± 0.7 and 10.2 ± 0.5, p < 0.001) and α-smooth muscle actin (4.1 ± 0.4 and 5.2 ± 0.4, p < 0.001). Both prevention and reversion by ANP were associated with downregulation of NF-ĸB (3.2 ± 0.4 and 2.8 ± 0.5, p < 0.001) and angiotensin II (8.2 ± 0.5 and 9.1 ± 0.7, p < 0.001) and diminished hypoxia evaluated through HIF-1α expression (8.4 ± 0.8 and 8.8 ± 0.7, p < 0.001). Conclusion: Our study provides evidence supporting a protective role of ANP in both prevention and reversion of renal inflammation in rats with acute sodium overload.