Leylliane de Fátima Leal Interaminense

Federal University of Pernambuco, Recife, Estado de Pernambuco, Brazil

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Publications (11)23.06 Total impact

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    ABSTRACT: The present study investigated the mechanisms underlying the vasorelaxant effects of the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in isolated superior mesenteric artery from spontaneously hypertensive rats (SHRs). At 0.1-1000 μg/mL, EOAC and NP relaxed SMA preparations pre-contracted with 75 mM KCl with IC(50) (geometric mean [95% confidence interval]) values of 294.19 [158.20-94.64] and 501.27 [378.60-624.00] μg/mL, respectively); or with phenylephrine (PHE) (IC(50)s = 11.07 [6.40-15.68] and 7.91 [4.08-11.74) μg/mL, respectively). All these effects were reversible and remained unaltered by vascular endothelium removal. In preparations maintained under Ca(2+)-free conditions, EOAC and NP (both at 600 μg/mL) reduced the PHE-, but not the caffeine-induced contraction. In Ca(2+)-free and high K(+) (75 mM) medium, the contractions produced by CaCl(2) or BaCl(2) were reduced or even abolished by EOAC and NP at 100 and 600 μg/mL, respectively. EOAC and NP (both at 10-1000 μg/mL) also relaxed the contraction evoked by phorbol dibutyrate (IC(50) = 52.66 [10.82-94.64] and 39.13 [31.55-46.72] μg/mL, respectively). It is concluded that NP has a myogenic endothelium-independent vasorelaxant effects and appears to be the active principle of the EOAC. Vasorelaxant effect induced by both EOAC and NP is preferential to receptor-activated pathways and it appears to occur intracellularly more than a superficial action restricted to the membrane environment such as a simple blocking activity on a given receptor or ion channel.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 01/2013; · 2.61 Impact Factor
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    ABSTRACT: This study investigated the cardiovascular responses to the essential oil of Aniba canelilla (EOAC) and its main constituent 1-nitro-2-phenylethane (NP) in spontaneously hypertensive rats (SHRs). In anesthetized SHRs, intravenous (i.v.) bolus injections of EOAC (1-20 mg/kg) or NP (1-10 mg/kg) elicited dose-dependent hypotensive and bradycardiac effects, which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by EOAC and NP both at 10 mg/kg was absent after left ventricle injection, fully abolished by bilateral vagotomy and perineural treatment of both cervical vagus nerves with capsaicin (250 μg/mL) while remained unaltered by i.v. pretreatment with capsazepine (1 mg/kg) or ondansetron (30 μg/kg). In conscious SHRs, NP (5 and 10 mg/kg, i.v.) evoked rapid hypotensive and bradycardiac effects (phase 1) that were fully abolished by methylatropine (1 mg/kg, i.v.) pretreatment. In rat endothelium-containing mesenteric preparations, increasing concentrations (0.1-1000 μg/mL) of EOAC and NP relaxed the phenylephrine-induced contraction in a concentration-dependent manner. It is concluded that NP induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. This effect does not appear to involve activation of either vanilloid TPRV(1) or 5-HT(3) receptors located on vagal sensory nerves. The phase 2 hypotensive response to i.v. NP seems to result, at least in part, from its direct vasodilatory effect on the peripheral smooth muscle. All in vivo and in vitro effects of EOAC are mostly attributed to the actions of its main constituent NP.
    Fundamental and Clinical Pharmacology 11/2010; 25(6):661-9. · 1.99 Impact Factor
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    ABSTRACT: Previously, it was shown that intravenous (i.v.) treatment with the essential oil of Aniba canelilla (EOAC) elicited a hypotensive response that is due to active vascular relaxation rather than to the withdrawal of sympathetic tone. The present study investigated mechanisms underlying the cardiovascular responses to 1-nitro-2-phenylethane, the main constituent of the EOAC. In pentobarbital-anesthetized normotensive rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) elicited dose-dependent hypotensive and bradycardiac effects which were characterized in two periods (phases 1 and 2). The first rapid component (phase 1) evoked by 1-nitro-2-phenylethane (10mg/kg) was fully abolished by bilateral vagotomy, perineural treatment of both cervical vagus nerves with capsaicin (250 microg/ml) and was absent after left ventricle injection. However, pretreatment with capsazepine (1mg/kg, i.v.) or ondansetron (30 microg/kg, i.v.) did not alter phase 1 of the cardiovascular responses to 1-nitro-2-phenylethane (10mg/kg, i.v.). In conscious rats, 1-nitro-2-phenylethane (1-10mg/kg, i.v.) evoked rapid hypotensive and bradycardiac (phase 1) effects that were fully abolished by methylatropine (1mg/kg, i.v.). It is concluded that 1-nitro-2-phenylethane induces a vago-vagal bradycardiac and depressor reflex (phase 1) that apparently results from the stimulation of vagal pulmonary rather than cardiac C-fiber afferents. The transduction mechanism of the 1-nitro-2-phenylethane excitation of C-fiber endings is not fully understood and does not appear to involve activation of either Vanilloid TPRV(1) or 5-HT(3) receptors. The phase 2 hypotensive response to 1-nitro-2-phenylethane seems to result, at least in part, from a direct vasodilatory effect since 1-nitro-2-phenylethane (1-300 microg/ml) induced a concentration-dependent reduction of phenylephrine-induced contraction in rat endothelium-containing aorta preparations.
    European journal of pharmacology 07/2010; 638(1-3):90-8. · 2.59 Impact Factor
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    ABSTRACT: Intravenous (i.v.) treatment of conscious DOCA-salt hypertensive rats with the essential oil of Ocimum gratissimum L. (Labiatae) (EOOG) induced a hypotensive effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone. To corroborate this hypothesis, the present study examined the vascular effects of EOOG and its main constituent, eugenol (EUG) and the putative mechanisms underlying these effects. Additionally, the role of the vascular beta(2)-adrenergic mechanism in the mediation of EOOG-induced hypotension has also been investigated. In conscious DOCA-salt hypertensive rats, the EOOG-induced hypotension was reversible and remained unchanged by i.v. pretreatment with propranolol (2 mg/kg). In isolated aorta preparations with intact endothelium from DOCA-salt hypertensive rats, EOOG (1-1000 microg/mL) and EUG (0.006-6 mM) relaxed the phenylephrine-induced contraction similarly with IC(50) [geometric mean (95% confidence interval)] values of 226.9 (147.8-348.3) microg/mL and 1.2 (0.6-2.1) mm, respectively. Vasorelaxant effects of EOOG were significantly altered by removal of the vascular endothelium [IC(50) = 417.2 (349.5-497.8) microg/mL]. In a calcium-free medium, the CaCl(2)-induced contractions were significantly reduced and even abolished by EOOG at 300 and 1000 microg/mL, respectively, whereas EOOG (1000 microg/mL) did not have any significant effect on caffeine-induced contractions. Similar results were obtained with EUG (1.8 and 6 mM) on both CaCl(2)- and caffeine-induced contractions, respectively. The data suggest that hypotensive responses to EOOG in DOCA-salt hypertensive rats are due to an active vascular relaxation, which is partly dependent upon the integrity of the vascular endothelium and seems predominantly mediated through an inhibition of plasmalemmal Ca(2+) influx rather than Ca(2+)-induced Ca(2+) release from the sarcoplasmic reticulum.
    Fundamental and Clinical Pharmacology 11/2007; 21(5):497-506. · 1.99 Impact Factor
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    ABSTRACT: Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of the bark of Aniba canelilla (EOAC) were investigated in normotensive rats. In both pentobarbital-anesthetized and conscious rats, i.v. bolus injections of EOAC (1 to 20 mg/kg) elicited similar and dose-dependent hypotension and bradycardia. Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardia without affecting the hypotension. In conscious rats, pretreatment with hexamethonium (30 mg/kg, i.v.) significantly reduced the EOAC-induced bradycardia without affecting the hypotension. The opposite effect was observed after i.v. pretreatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl esther (L-NAME, 20 mg/kg). However, both EOAC-induced hypotension and bradycardia were significantly reduced by pretreatment with methylatropine (1 mg/kg, i.v.). In rat endothelium-containing aorta preparations, EOAC (1-600 microg/mL) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC50 (geometric mean+/-95% confidence interval)=64.5 (45.6-91.2) microg/mL)], an effect that was significantly reduced by the addition of atropine (10 microM) in the perfusion medium [IC50=109.5 (72.5-165.4) microg/mL)]. Furthermore, the vasorelaxant effects of the EOAC were also but significantly reduced [IC50=139.1 (105.2-183.9) microg/mL)] by removal of the vascular endothelium. Furthermore, the CaCl2-induced contractions in calcium-free medium were reduced and even fully abolished by EOAC (100 and 600 microg/mL), respectively. However, EOAC (600 microg/mL) was without significant effect on caffeine-induced contractions in calcium-free medium. These data show that i.v. treatment of rats with EOAC induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears mainly dependent upon the presence of an operational and functional parasympathetic drive to the heart. However, the hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. This relaxation seems partly mediated by an endothelial L-arginine/nitric oxide pathway through peripheral muscarinic receptor activation (endothelium-dependent relaxation) and predominantly through an inhibition of calcium inward current (endothelium-independent relaxation).
    Journal of Cardiovascular Pharmacology 11/2005; 46(4):412-21. · 2.38 Impact Factor
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    ABSTRACT: The cardiovascular effects of intravenous (i.v.) treatment with the essential oil of Ocimum gratissimum (EOOG) and its main constituent, eugenol (Eug) were investigated in the experimental model of deoxycorticosterone acetate (DOCA-salt)-hypertensive rats. In both conscious DOCA-salt hypertensive rats and their uninephrectomized controls, i.v. bolus injections of EOOG (1 - 20 mg/kg) or Eug (1 - 10 mg/kg) induced dose-dependent hypotension and bradycardia. Treatment with DOCA-salt significantly enhanced the maximal decreases in mean aortic pressure (MAP) elicited by hexamethonium (30 mg/kg, i.v.) as well as the hypotensive responses to both EOOG and Eug without affecting the bradycardia. However, the enhancement of EOOG-induced hypotension in hypertensive rats remained unaffected by i.v. pretreatment with either hexamethonium (30 mg/kg) or methylatropine (1 mg/kg). These results show that i.v. treatment with EOOG or Eug dose-dependently decreased blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement appears related mainly to an increase in EOOG-induced vascular smooth relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model.
    Planta Medica 05/2005; 71(4):376-8. · 2.35 Impact Factor
  • Saad Lahlou, Leylliane de Fátima Leal Interaminense, André Fernandes Figueiredo, Glória Pinto Duarte
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    ABSTRACT: In conscious rats, intravenous treatment with the dopamine D2-like receptor agonist quinpirole, elicited a pressor effect, which is attributed to central dopamine D2 receptor-mediated activation of sympathetic outflow associated with arginine vasopressin release. This prominent central effect is opposed to peripheral sympathoinhibitory and spinal depressor effects. The present study investigated the effects of pre- and postnatal undernutrition on the central pressor responsiveness to quinpirole. Malnourished (MalN) rats were obtained by feeding dams a multideficient diet (providing 8% protein) during pregnancy and nursing. At 90 days of age, MalN rats weighed significantly less than control (CNT) rats born to dams fed standard commercially diet (23% protein) during pregnancy and nursing. Baseline mean arterial pressure and heart rate in MalN rats were comparable to those of CNT. Intravenous treatment with quinpirole (0.3 mg/kg) in MalN conscious rats induced a pressor effect, which was significantly reduced in both magnitude and duration, when compared with CNT rats. In both groups studied, pressor response to quinpirole was fully abolished by the peripheral and central dopamine D2 receptor antagonist, metoclopramide (5 mg/kg, i.v.) whereas was significantly enhanced after pretreatment with either intravenous (0.5 mg/kg) or intrathecal (40 microg per rat at T9-T10 level) domperidone, a dopamine D2 receptor antagonist that does not cross the blood-brain barrier. However, even under peripheral and spinal dopamine D2 receptor blockade, maximum pressor effect of quinpirole remained significantly reduced in MalN when compared with CNT rats. Neither the maximum pressor nor the bradycardiac responses to intravenous phenylephrine or arginine vasopressin differed between CNT and MalN rats. This study shows that undernutrition imposed during fetal life and suckling blunted the pressor response to quinpirole in conscious rats. This blunted response appears mainly related to desensitization of brain dopamine D2 receptors rather than enhanced peripheral and/or spinal dopamine D2 receptor-mediated depressor effect or vascular hyporesponsiveness to alpha1-adrenoceptor and vasopressin receptor stimulation.
    Journal of Cardiovascular Pharmacology 08/2004; 44(1):16-25. · 2.38 Impact Factor
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    ABSTRACT: 1. The cardiovascular effects of intravenous (i.v.) administration of the essential oil of Ocimum gratissimum (EOOG) were investigated in rats. In addition, the present study examined: (i) whether the autonomic nervous system is involved in the mediation of EOOG-induced changes in mean aortic pressure (MAP) and heart rate (HR); and (ii) whether these changes could be attributed, at least in part, to the actions of eugenol, the major constituent of EOOG. 2. In both pentobarbitone-anaesthetized and conscious rats, i.v. bolus injections of EOOG (1-20 mg/kg) elicited immediate and dose-dependent decreases in MAP and HR. These responses to EOOG were of the same order of magnitude irrespective of whether the animal was under general anaesthesia. 3. Pretreatment of anaesthetized rats with bilateral vagotomy did not significantly modify the EOOG-induced dose-dependent hypotension, whereas it significantly reduced the bradycardia at the highest dose used. 4. In conscious rats, i.v. injections of bolus doses (1-10 mg/kg) of eugenol also elicited immediate and dose-dependent decreases in MAP and HR. Intravenous pretreatment of conscious rats with either methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) significantly reduced the EOOG-induced dose-dependent bradycardia without affecting the hypotension. 5. These data show, for the first time, that i.v. administration of EOOG to either anaesthetized or conscious rats induces an immediate and significant hypotension and bradycardia, which appear to be due, at least in part, to the actions of the major constituent of EOOG, eugenol. These cardiovascular effects appear to be mediated by different pathways because only EOOG-induced hypotension appears to be independent of the presence of an operational autonomic nervous system. This may suggest that the hypotensive activity of EOOG results from its vasodilatory effects directly upon vascular smooth muscle.
    Clinical and Experimental Pharmacology and Physiology 05/2004; 31(4):219-25. · 2.41 Impact Factor
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    ABSTRACT: Cardiovascular effects of intravenous (i.v.) treatment with eugenol (Eug), a natural pungent present in many plant essential oils, were investigated in normotensive rats. In either anesthetized or conscious rats, i.v. bolus injections of Eug (1 to 10 mg/kg) elicited immediate and dose-dependent hypotension and bradycardia. Magnitude of Eug-induced hypotension was similar in both groups. Pretreatment of anesthetized rats with bilateral vagotomy almost abolished the bradycardic responses to Eug without affecting the hypotension. Likewise, i.v. pretreatment of conscious rats with methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) significantly reduced the Eug-induced bradycardia without affecting the hypotension. However, i.v. pretreatment with the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl (L-NAME, 20 mg/kg), affected neither the hypotension nor the bradycardia elicited by Eug. In rat mesenteric bed preparations precontracted with potassium (60 mM), Eug (0.1-2 mM) induced a reversible and concentration-dependent vasodilator effect, which remained unaffected by atropine (1 microM). These results show that i.v. treatment of rats with Eug induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears dependent upon the presence of an intact and functional parasympathetic nerve drive to the heart while the hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. Released nitric oxide from vascular endothelial cells seems to be not involved in the mediation of Eug-induced hypotension.
    Journal of Cardiovascular Pharmacology 03/2004; 43(2):250-7. · 2.38 Impact Factor
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    Saad Lahlou, Leylliane Fátima Leal Interaminense, José Henrique Leal-Cardoso, Gloria Pinto Duarte
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    ABSTRACT: The present study investigated the hypotensive responses to intravenous (i.v.) treatment with the essential oil of Alpinia zerumbet (EOAZ) and its main constituent, terpinen-4-ol (Trp-4-ol), in the experimental model of deoxycorticosterone-acetate (DOCA)-salt hypertensive rat. In both DOCA-salt hypertensive and uninephrectomized, normotensive rats, i.v. bolus injections of EOAZ (1-20 mg/kg) or Trp-4-ol (1-10 mg/kg) decreased mean aortic pressure (MAP) in a dose-related manner. However, hypotensive responses to Trp-4-ol were significantly greater than those evoked by the same doses of EOAZ (1-10 mg/kg). Treatment with DOCA-salt significantly enhanced the maximal percentage decreases in MAP evoked by EOAZ or Trp-4-ol. Likewise, both maximal percentage and absolute decreases in MAP elicited by i.v. injection of the ganglion blocker, hexamethonium (30 mg/kg), were significantly greater in DOCA-salt hypertensive than in control rats. In DOCA-salt hypertensive rats, neither hexamethonium (30 mg/kg, i.v.) nor methylatropine (1 mg/kg, i.v.) pretreatment affected the enhancement of EOAZ-induced hypotension. These results show that i.v. treatment with either EOAZ or Trp-4-ol dose-dependently decreases blood pressure in conscious DOCA-salt hypertensive rats, and this action is enhanced when compared with uninephrectomized controls. This enhancement could be related mainly to an increase in EOAZ-induced vascular smooth muscle relaxation rather than to enhanced sympathetic nervous system activity in this hypertensive model. The data further support our previous hypothesis that hypotensive effects of EOAZ are partially attributed to the actions of Trp-4-ol.
    Fundamental and Clinical Pharmacology 07/2003; 17(3):323-30. · 1.99 Impact Factor
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    Saad Lahlou, Paula F Araújo Lima, Leylliane F L Interaminense, Gloria Pinto Duarte
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    ABSTRACT: Bromocriptine-induced tachycardia, persisting after adrenalectomy, is mediated by central dopamine D2 receptor stimulation through activation of the sympathetic outflow to the heart. The present study investigated the effects of malnutrition during pregnancy on bromocriptine-induced tachycardia in adult conscious rats. Malnourished rats were obtained by feeding dams a multideficient diet (providing 8% protein) during mating and pregnancy. Birth weight was significantly reduced in malnourished rats when compared to control rats born to dams fed standard commercially diet (23% protein) during mating and pregnancy. Baseline mean aortic pressure and heart rate in malnourished rats were comparable to those of well-nourished rats. Tachycardia (33+/-9 beats/min.), but not the hypotensive response to intravenous bromocriptine (150 microg/kg) was significantly reduced in malnourished rats, compared with control rats (70+/-10 beats/min.). In malnourished rats, pretreatment with intravenous domperidone (500 microg/kg) blocked the bromocriptine-induced hypotension, without affecting the tachycardia. Neither cardiac vagal (40+/-6 beats/min.) nor sympathetic tone (76+/-6 beats/min.) was significantly altered by multideficient diet-induced malnutrition (51+/-6 and 67+/-10 beats/min., respectively). In isolated perfused heart preparations from malnourished rats, positive inotropic response to isoproterenol (10-8 to 10-4 M) was not significantly different compared to that in control rats. In summary, malnutrition during foetal life blunted the bromocriptine-induced tachycardia, an effect that could be related to central dopamine D2 receptor desensitization rather than to impairment of autonomic regulation of the heart or cardiac beta-adrenoceptor desensitization.
    Pharmacology &amp Toxicology 05/2003; 92(4):189-94.