Leylliane de Fátima Leal Interaminense

Antihypertensive effects of the essential oil of Alpinia zerumbet and its main constituent, terpinen-4-ol, in DOCA-salt hypertensive conscious rats

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.

Pharmacological evidence of calcium-channel blockade by essential oil of Ocimum gratissimum and its main constituent, eugenol, in isolated aortic rings from DOCA-salt hypertensive rats

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 β2‐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 μg/mL) and EUG (0.006–6 mm) relaxed the phenylephrine‐induced contraction similarly with IC50 [geometric mean (95% confidence interval)] values of 226.9 (147.8–348.3) μg/mL and 1.2 (0.6–2.1) mm, respectively. Vasorelaxant effects of EOOG were significantly altered by removal of the vascular endothelium [IC50 = 417.2 (349.5–497.8) μg/mL]. In a calcium‐free medium, the CaCl2‐induced contractions were significantly reduced and even abolished by EOOG at 300 and 1000 μg/mL, respectively, whereas EOOG (1000 μg/mL) did not have any significant effect on caffeine‐induced contractions. Similar results were obtained with EUG (1.8 and 6 mm) on both CaCl2‐ 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 Ca2+ influx rather than Ca2+‐induced Ca2+ release from the sarcoplasmic reticulum.

Cardiovascular effects of the essential oil of Aniba canelilla bark in normotensive rats.

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, NG-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 μg/mL) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC50 (geometric mean ± 95% confidence interval) = 64.5 (45.6-91.2) μg/mL)], an effect that was significantly reduced by the addition of atropine (10 μM) in the perfusion medium [IC50 = 109.5 (72.5-165.4) μg/mL)]. Furthermore, the vasorelaxant effects of the EOAC were also but significantly reduced [IC50 = 139.1 (105.2-183.9) μg/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 μg/mL), respectively. However, EOAC (600 μg/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).

Cardiovascular effects of eugenol, a phenolic compound present in many plant essential oils, in normotensive rats.

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 &mgr;M). 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.

1-Nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, elicits a vago-vagal bradycardiac and depressor reflex in normotensive rats

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.

CARDIOVASCULAR EFFECTS OF THE ESSENTIAL OIL OF OCIMUM GRATISSIMUM LEAVES IN RATS: ROLE OF THE AUTONOMIC NERVOUS SYSTEM

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.

Vasorelaxant effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in superior mesenteric arteries from spontaneously hypertensive rats.

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 mMKCl 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.

Cardiovascular effects of 1-nitro-2-phenylethane, the main constituent of the essential oil of Aniba canelilla, in spontaneously hypertensive rats.

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 TPRV1 or 5‐HT3 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.

Cardiovascular effects of a labdenic diterpene isolated from Moldenhawera nutans in conscious, spontaneously hypertensive rats

Abstract Context: The labdenic diterpene labd-8(17)-en-15-oic acid (labd-8) isolated from a methanolic extract of Moldenhawera nutans Queiroz & Alkin (Leguminosae) has hypotensive and tachycardiac properties in normotensive rats. A part of the hypotensive effect was due to a reduction in the sympathetic nerve drive to vessels, an event admittedly enhanced in spontaneously hypertensive rats (SHRs). Objectives: We assessed whether the cardiovascular effects induced by labd-8 could be enhanced in SHRs. Materials and methods: For in vivo experiments, arterial and venous catheters were implanted under anesthesia for blood pressure recording and drug administration, respectively. For in vitro experiments, thoracic aorta rings were suspended in organ baths containing warm (37 °C) perfusion medium that was continuously bubbled with carbogen. Results: Intravenous injection of labd-8 (1, 3, 5, and 10 mg/kg) induced similar dose-dependent hypotension and tachycardia in both SHRs and Wistar–Kyoto rats (WKY). In SHRs, only the tachycardia response to labd-8 was significantly reduced by pretreatment with methylatropine or propranolol. However, both cardiovascular effects of labd-8 were reduced by hexamethonium while remained unchanged by l-NAME. In isolated aortic preparations from SHRs, labd-8 (1–1000 µg/mL) relaxed potassium-induced contractions with an IC50 (geometric mean [95% confidence interval]) value (536.5 [441.0–631.9] µg/mL) significantly greater than that (157.6 [99.1–250.5] µg/mL) obtained in preparations from WKY rats. Conclusion: In SHRs, the hypotension induced by labd-8 is associated with a reflex tachycardia and seems mediated partly through withdrawal of sympathetic vasomotor tone and partly through an active vasorelaxation. Its magnitude was not enhanced when compared with WKY rats likely because of impaired vasorelaxant effects of labd-8 in preparations from SHRs.

Pressor responsiveness to intravenous quinpirole is blunted in malnourished, conscious rats: Central vs. peripheral and spinal mechanisms

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 μg 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 &agr;1-adrenoceptor and vasopressin receptor stimulation.