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      Evaluation of the cardiovascular effects of vasicine, an alkaloid isolated from the leaves of Sida cordifolia L. (Malvaceae)

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          Abstract

          The cardiovascular effects of vasicine, an alkaloid isolated from the leaves of Sida cordifolia L., were evaluated in this work. In non-anaesthetized rats (n=6), vasicine (1, 2.5, 5 and 10 mg/kg; i.v., randomly) induced hypotension associated with an intense bradycardia. Both responses were completely abolished after atropine (2mg/Kg; i.v.) and attenuated after hexamethonium (20 mg/Kg; i.v.). In isolated rat mesenteric artery rings, vasicine (0.03, 0.1, 0.3, 1, 3, 10, 30, 100 and 300 μg/mL, cumulatively) induced concentration-dependent relaxation of phenylephrine-induced tone (IC50= 3.8±0.9 μg/mL; n = 6). In conclusion, the results show that vasicine produce hypotension and bradycardia which appears to be due to the stimulation of cardiac muscarinic receptors (directly and/or indirectly), and by a decrease of the peripheral resistances.

          Translated abstract

          Os efeitos cardiovasculares de vasicina, um alcalóide isolado das folhas de Sida cordifolia L., foi avaliado neste trabalho. Em ratos não-anestesiados (n=6), vasicina (1, 2.5, 5 e 10 mg/kg; i.v., aleatoriamente) induziu hipotensão associada com uma intensa bradicardia. Ambas as respostas buscaram completamente abolidas após atropina (2 mg/Kg; i.v.) e atenuadas após hexamethonio (20 mg/Kg; i.v.). Em anéis de artéria mesentérica de rato isolada, vasicina (0.03, 0.1, 0.3, 1, 3, 10, 30, 100 e 300 g/mL, cumulativamente) induziu relaxamento concentração-dependente de tônus promovido por fenilefrina (IC50= 3.8 0.9 g/mL; n= 6). Em conclusão, os resultados mostram que vasicina produz hipotensão e bradicardia que parecem ser devidas à excitação de receptores muscarínicos cardíacos (direta e/ou indiretamente) e por uma diminuição das resistências periféricas.

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          Significant role of neuronal non-N-type calcium channels in the sympathetic neurogenic contraction of rat mesenteric artery.

          1. The possible involvement of pre-junctional non-N-type Ca2+ channels in noradrenaline (NA)-mediated neurogenic contraction by electrical field stimulation (EFS) was examined pharmacomechanically in the isolated rat mesenteric artery. 2. EFS-generated contraction of endothelium-denuded mesenteric artery was frequency-dependent (2 - 32 Hz) and was abolished by tetrodotoxin (TTX, 1 microM), guanethidine (5 microM) or prazosin (100 nM), indicating that NA released from sympathetic nerve endings mediates the contractile response. 3. NA-mediated neurogenic contractions to lower frequency stimulations (2 - 8 Hz) were almost abolished by an N-type Ca2+ channel blocker, omega-conotoxin-GVIA (1 microM) whereas the responses to higher frequency stimulations (12 - 32 Hz) were less sensitive to omega-conotoxin-GVIA. The omega-conotoxin-GVIA-resistant component of the contractile response to 32 Hz stimulation was inhibited partly (10 - 20%) by omega-agatoxin-IVA (10 - 100 nM; concentrations which are relatively selective for P-type channels) and to a greater extent by omega-agatoxin-IVA (1 microM) and omega-conotoxin-MVIIC (3 microM), both of which block Q-type channels at the concentrations used. 4. omega-Agatoxin-IVA (10 - 100 nM) alone inhibited 32 Hz EFS-induced contraction by 10 approximately 20% whereas omega-conotoxin-MVIIC (3 microM) alone inhibited the response by approximately 60%. 5. These omega-toxin treatments did not affect the contractions evoked by exogenously applied NA. 6. These findings show that P- and Q-type as well as N-type Ca2+ channels are involved in the sympathetic neurogenic vascular contraction, and suggest the significant role of non-N-type Ca2+ channels in NA release from adrenergic nerve endings when higher frequency stimulations are applied to the nerve.
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            Potent uterine activity of alkaloid vasicine.

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              Purification of the muscarinic acetylcholine receptor from porcine atria.

              The muscarinic acetylcholine receptor from porcine atria has been purified 100,000-fold to homogeneity by solubilization in digitonin/cholate and sequential chromatography on wheat germ agglutinin-agarose, diethylaminoethylagarose, hydroxylapatite, and 3-(2'-aminobenzhydryloxy)tropane-agarose. The yield of purified receptor was 4.3% of that found in the membrane fraction, and the purified receptor bound 11.1-12.8 nmol of L-[3H]quinuclidinyl benzilate per mg of protein, corresponding to a binding component Mr of 78,400-90,000. The purified receptor preparation consisted of two polypeptides in approximately equimolar amounts when examined on silver-stained sodium dodecyl sulfate/polyacrylamide gels. The larger polypeptide (Mr 78,000 on 8% polyacrylamide gels) was specifically alkylated with [3H]propylbenzilylcholine mustard, whereas the smaller polypeptide (Mr 14,800) was not labeled. The possibility that the small polypeptide is a contaminant fortuitously appearing in equimolar amounts with the large polypeptide cannot be ruled out at this time. The purified preparation was highly stable, with no measurable change in the number of ligand binding sites or the gel pattern after 1 month's storage on ice. Scatchard analysis showed a single class of binding sites for the antagonist L-[3H]quinuclidinyl benzilate with a dissociation constant of 61 +/- 4 pM. Equilibrium titration experiments demonstrated that the antagonist L-hyoscyamine displaced L-[3H]quinuclidinyl benzilate from a single class of sites (Kd = 475 +/- 30 pM), whereas the agonist carbamoylcholine interacted at two populations of sites (53% +/- 3% high affinity, Kd = 1.1 +/- 0.3 microM; 47% +/- 3% low affinity, Kd = 67 +/- 14 microM). The ligand binding data were very similar to that for the membrane-bound receptor, suggesting that the receptor has not been altered radically during purification.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Role: ND
                Journal
                rbfar
                Revista Brasileira de Farmacognosia
                Rev. bras. farmacogn.
                Sociedade Brasileira de Farmacognosia (Curitiba )
                1981-528X
                2003
                : 13
                : suppl 2
                : 37-39
                Affiliations
                [1 ] Universidade Federal da Paraíba Brazil
                Article
                S0102-695X2003000400012
                10.1590/S0102-695X2003000400012
                90c967b6-e45d-49f8-b58a-477c0ff2acbd

                http://creativecommons.org/licenses/by/4.0/

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                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=0102-695X&lng=en
                Categories
                PHARMACOLOGY & PHARMACY

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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