No abstract

It has been established that oximes cause endothelium-independent relaxation in blood vessels. In the present study, the cardiovascular effects of the new oxime 3-hydroxy-4-(hydroxyimino)-2-(3-methylbut-2-enylnaphtalen-1(4H)-one (Oxime S1) derived from lapachol were evaluated. In normotensive rats, administration of Oxime S1 (10,15, 20 and 30 mg/Kg, i.v.) produced dose-dependent reduction in blood pressure. In isolated aorta and superior mesenteric artery rings, Oxime S1 induced endothelium-independent and concentration-dependent relaxations (10 −8 M to 10 −4 M). In addition, Oxime S1-induced vasorelaxations were attenuated by hydroxocobalamin or methylene blue in aorta and by PTIO or ODQ in mesenteric artery rings, suggesting a role for the nitric oxide (NO) pathway. Additionally, Oxime S1 (30 and 100 µM) significantly increased NO concentrations (13.9 ± 1.6 nM and 17.9 ± 4.1 nM, respectively) measured by nitric oxide microsensors. Furthermore, pre-contraction with KCl (80 mM) prevented Oxime S1-derived vasorelaxation in endothelium-denuded aortic rings. Of note, combined treatment with potassium channel inhibitors also reduced Oxime S1-mediated vasorelaxation suggesting OPEN ACCESSMolecules 2014, 19 9774 a role for potassium channels, more precisely K ir , K v and K ATP channels. We observed the involvement of BK Ca channels in Oxime S1-induced relaxation in mesenteric artery rings.In conclusion, these data suggest that the Oxime S1 induces hypotension and vasorelaxation via NO pathway by activating soluble guanylate cyclase (sGC) and K + channels.

This study aimed to investigate the cardiovascular effects elicited by Dictyota pulchella, a brown alga, using in vivo and in vitro approaches. In normotensive conscious rats, CH2Cl2/MeOH Extract (CME, 5, 10, 20 and 40 mg/kg) from Dictyota pulchella produced dose-dependent hypotension (−4 ± 1; −8 ± 2; −53 ± 8 and −63 ± 3 mmHg) and bradycardia (−8 ± 6; −17 ± 11; −257 ± 36 and −285 ± 27 b.p.m.). In addition, CME and Hexane/EtOAc Phase (HEP) (0.01–300 μg/mL) from Dictyota pulchella induced a concentration-dependent relaxation in phenylephrine (Phe, 1 μM)-pre-contracted mesenteric artery rings. The vasorelaxant effect was not modified by the removal of the vascular endothelium or pre-incubation with KCl (20 mM), tetraethylammonium (TEA, 3 mM) or tromboxane A2 agonist U-46619 (100 nM). Furthermore, CME and HEP reversed CaCl2-induced vascular contractions. These results suggest that both CME and HEP act on the voltage-operated calcium channel in order to produce vasorelaxation. In addition, CME induced vasodilatation after the vessels have been pre-contracted with L-type Ca2+ channel agonist (Bay K 8644, 200 nM). Taken together, our data show that CME induces hypotension and bradycardia in vivo and that both CME and HEP induce endothelium-independent vasodilatation in vitro that seems to involve the inhibition of the Ca2+ influx through blockade of voltage-operated calcium channels.

No abstract

The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy). In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS), indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

Introduction: One of the stages of women's lives is the climacteric, a period often accompanied by emotional and physical signs and emotional, which may negatively influence the quality of life. Among the typical climacteric symptoms are sleep disorders, often overlooked by professionals who assist the woman.

A paralisia periódica hipocalêmica é uma doença neuromuscular, au­tossômica dominante, caracterizada por ataques episódicos de parali­sia flácida acompanhado de hipocalemia. As mutações nos canais de cálcio operados por voltagem (Cav) causam paralisia periódica hipo­calêmica tipo 1, nesta, apresentando atividade elétrica do músculo re­duzida ou mesmo ausente durante os ataques, provavelmente por uma falha na excitação-contração. Possivelmente pode haver envolvimento de canais para potássio sensíveis a ATP. Os sintomas desta geralmente começam na primeira ou segunda década de vida. Objetivo. Analisar o pa¬pel dos canais iônicos na fisiopatologia da paralisia periódica hi­pocalêmica tipo 1. Método. Tratou-se de um trabalho de revisão de literatura. Foram utilizados livros e artigos publicados na base de da­dos Pubmed, Science Direct e Scielo nas línguas portuguesa e inglesa. Resultados. Foram selecionados 36 trabalhos, dentre eles 34 artigos científicos e 02 livros. Conclusão. Apesar do considerável progresso, ainda é pouco compreendido a fisiopatologia dos genes mutantes nas canalopatias musculares, tais como na paralisia periódica, fazendo-se necessário direcionar esforços não só para a detecção de novos genes causadores e novas mutações, mas também para suas consequências fi­siopatológicas. A elucidação precisa da fisiopatologia é necessária para abrir novas perspectivas para futuras abordagens terapêuticas.

Benzoyltryptamine analogues act as neuroprotective and spasmolytic agents on smooth muscles. In this study, we investigated the ability of N-salicyloyltryptamine (STP) to produce vasorelaxation and determined its underlying mechanisms of action. Isolated rat mesenteric arteries with and without functional endothelium were studied in an isometric contraction system in the presence or absence of pharmacological inhibitors. Amperometric experiments were used to measure the nitric oxide (NO) levels in CD31+ cells using flow cytometry. GH3 cells were used to measure Ca2+ currents using the whole cell patch clamp technique. STP caused endothelium-dependent and -independent relaxation in mesenteric rings. The endothelial-dependent relaxations in response to STP were markedly reduced by L-NAME (endothelial NO synthase—eNOS—inhibitor), jHydroxocobalamin (NO scavenger, 30 µM) and ODQ (soluble Guanylyl Cyclase—sGC—inhibitor, 10 µM), but were not affected by the inhibition of the formation of vasoactive prostanoids. These results were reinforced by the increased NO levels observed in the amperometric experiments with freshly dispersed CD31+ cells. The endothelium-independent effect appeared to involve the inhibition of voltage-gated Ca2+ channels, due to the inhibition of the concentration-response Ca2+ curves in depolarizing solution, the increased relaxation in rings that were pre-incubated with high extracellular KCl (80 mM), and the inhibition of macroscopic Ca2+ currents. The present findings show that the activation of the NO/sGC/cGMP pathway and the inhibition of gated-voltage Ca2+ channels are the mechanisms underlying the effect of STP on mesenteric arteries.